Dyne Therapeutics, Inc. (Nasdaq: DYN), a muscle disease company
focused on advancing innovative life-transforming therapeutics for
people living with genetically driven diseases, today announced new
preclinical data from its myotonic dystrophy type 1 (DM1) program
demonstrating robust RNA knockdown of toxic human nuclear DMPK, the
genetic basis of the disease.
Dyne’s FORCE™ platform leverages the importance of
transferrin 1 receptor, TfR1, in muscle biology as the
foundation for its novel approach. TfR1, which is highly expressed
on the surface of muscle cells, is required for iron transport into
muscle cells. Dyne links therapeutic payloads to its TfR1-binding
fragment antibody (Fab) to develop targeted therapeutics for muscle
diseases. Dyne’s DM1 lead candidate consists of a Fab conjugated to
an antisense oligonucleotide (ASO) to enable targeted delivery to
muscle tissue to reduce accumulation of toxic DMPK RNA in the
nucleus, release splicing proteins, allow normal mRNA processing
and translation of normal proteins, and potentially stop or reverse
the disease.
These new preclinical data build on previous results showing
significant reduction in cytoplasmic wild type DMPK RNA in a mouse
model that expresses human TfR1(hTfR1). To assess the ability of
its lead DM1 candidate to reduce toxic human nuclear DMPK RNA, Dyne
developed an innovative hTfR1/DMSXL mouse model that expresses the
human TfR1 and carries a human DMPK gene that represents a severe
DM1 phenotype with more than 1,000 CTG repeats. In this model, two
doses (2 x 10 mg/kg) of Dyne’s candidate resulted in significant
toxic human nuclear DMPK knockdown at 14 days: 60 percent in the
heart; 56 percent in the diaphragm; 54 percent in the tibialis
anterior and 39 percent in the gastrocnemius. In the study, Dyne’s
candidate was well tolerated. Dyne expects to share data from the
hTfR1/DMSXL model at a scientific meeting during 2021.
“At Dyne we are focused on developing therapies designed to
target the genetic basis of the disease with the goal of delivering
disease modification for patients,” said Romesh Subramanian, Ph.D.,
chief scientific officer of Dyne. “Multiple genetic studies in DM1
have suggested that a 30 to 50 percent knockdown of toxic human
DMPK has the potential to be disease modifying. We are very pleased
with the robust toxic human DMPK reduction observed in the
hTfR1/DMSXL model, which, along with our previous preclinical data
showing correction of splicing and reversal of myotonia, indicates
the potential to have an impact for patients living with a disease
with no approved therapies. We intend to utilize this novel model
to conduct IND-enabling work as we progress toward the clinic.”
“In DM1, it is critical to target the nucleus where the
disease-causing toxic DMPK resides and forms foci,” said Valeria
Sansone, M.D., Ph.D., Clinical and Scientific Director, Clinical
Center NeMO, Milan; Associate Professor of Neurology, University of
Milan. “The innovative preclinical model used in this study has the
potential for translation into human disease. The data demonstrate
compelling reduction in levels of DMPK RNA and suggest this
approach may be effective in targeting nuclear DMPK and delivering
a therapeutic to muscle for diseases such as DM1.”
The new preclinical data from the hTfR1/DMSXL model are included
in an updated corporate presentation available in the Investors
& Media section of the Company’s website and add to the robust
in vitro and in vivo findings generated previously in Dyne’s DM1
program:
- Reduction in nuclear foci and correction of splicing in DM1
patient cells
- Correction of splicing and reversal of myotonia in
well-validated HSALR model
- Enhanced muscle distribution as evidenced by reduced levels of
cytoplasmic wild type DMPK RNA in non-human primates (NHPs)
- Durability of response of up to 12 weeks after a single dose in
a wild type mouse model
- Favorable tolerability observed in multiple NHP studies
“Today’s exciting data further validate our FORCE platform which
drives our efforts to deliver targeted, modern oligonucleotide
therapies with the potential to be life-transforming for patients
with serious muscle diseases,” said Joshua Brumm, president and
chief executive officer of Dyne. “We remain on track to submit INDs
for our three programs between the fourth quarter of 2021 and the
fourth quarter of 2022, with DM1 and DMD submissions anticipated in
the earlier part of that window, followed later by FSHD.”
About Myotonic Dystrophy Type 1 (DM1)
DM1 is a rare, progressive, genetic disease that affects
skeletal, cardiac and smooth muscles. It is a monogenic, autosomal
dominant disease caused by an abnormal expansion in a region of
the DMPK gene. The expansion in the number of CTG triplet
repeats causes toxic RNA to cluster in the nucleus, forming nuclear
foci and altering the splicing of multiple proteins essential for
normal cellular function. This altered splicing results in a wide
range of symptoms. People living with DM1 typically experience
progressive weakness of major muscle groups, which can affect
mobility, breathing, heart function, speech, digestion and vision
as well as cognition. DM1 is estimated to affect more than 40,000
people in the United States and over 74,000 people in Europe, but
there are currently no approved disease-modifying therapies.
About Dyne Therapeutics
Dyne Therapeutics is building a leading muscle disease company
focused on advancing innovative life-transforming therapeutics for
people living with genetically driven diseases. The Company is
utilizing its proprietary FORCE™ platform to overcome the current
limitations of muscle tissue delivery with modern oligonucleotide
therapeutic candidates. Dyne is developing a broad portfolio of
therapeutics for muscle diseases, including programs in myotonic
dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and
facioscapulohumeral muscular dystrophy (FSHD). For more
information, please visit www.dyne-tx.com, and follow us
on Twitter, LinkedIn and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements that
involve substantial risks and uncertainties. All statements, other
than statements of historical facts, contained in this press
release, including statements regarding Dyne’s strategy, future
operations, prospects, plans, objectives of management, the
expected timeline for submitting investigational new drug
applications, the potential advantages of Dyne’s FORCE platform and
programs, expectations regarding the translation of preclinical
findings to human disease and plans to conduct additional
preclinical studies, constitute forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. The words “anticipate,” “believe,” “continue,” “could,”
“estimate,” “expect,” “intend,” “may,” “might,” “objective,”
“ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or
“would,” or the negative of these terms, or other comparable
terminology are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words. Dyne may not actually achieve the plans,
intentions or expectations disclosed in these forward-looking
statements, and you should not place undue reliance on these
forward-looking statements. Actual results or events could differ
materially from the plans, intentions and expectations disclosed in
these forward-looking statements as a result of various important
factors, including: uncertainties inherent in the identification
and development of product candidates, including the conduct of
research activities, the initiation and completion of preclinical
studies and clinical trials; uncertainties as to the availability
and timing of results from preclinical studies; the timing of and
Dyne’s ability to submit and obtain regulatory approval for
investigational new drug applications; whether results from
preclinical studies will be predictive of the results of later
preclinical studies and clinical trials; Dyne’s ability to obtain
sufficient cash resources to fund the Company’s foreseeable and
unforeseeable operating expenses and capital expenditure
requirements; the impact of the COVID-19 pandemic on Dyne’s
business and operations; as well as the risks and uncertainties
identified in Dyne’s filings with the Securities and Exchange
Commission (SEC), including the Company’s most recent Form 10-Q and
in subsequent filings Dyne may make with the SEC. In addition, the
forward-looking statements included in this press release represent
Dyne’s views as of the date of this press release. Dyne anticipates
that subsequent events and developments will cause its views to
change. However, while Dyne may elect to update these
forward-looking statements at some point in the future, it
specifically disclaims any obligation to do so. These
forward-looking statements should not be relied upon as
representing Dyne’s views as of any date subsequent to the date of
this press release.
Contact:
Dyne TherapeuticsAmy Reillyareilly@dyne-tx.com 857-341-1203
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