Design Therapeutics Announces Positive Preclinical Data Highlighting Disease-Modifying Potential of its Novel DM1 GeneTACs as a Treatment for Myotonic Dystrophy Type-1
September 08 2021 - 6:30AM
Design Therapeutics, Inc. (Nasdaq: DSGN), a biotechnology company
developing small molecule treatments for degenerative genetic
disorders, today announced new preclinical data from its novel DM1
GeneTAC™ program, which demonstrated a near-complete
resolution of disease-causing foci and correction of splicing
defects in myotonic dystrophy type-1 (DM1) patient cells. These
data will be presented in a poster titled “Small molecule GeneTACs
reduce toxic nuclear foci and correct splicing defects in multiple
DM1 cell types,” at the 2021 Virtual Myotonic Dystrophy Foundation
Annual Conference, being held virtually from September 10-11, 2021.
“DM1 is a devastating multi-system genetic disorder caused by a
nucleotide repeat expansion in the DMPK gene that leads to
progressive muscle weakness, and also affects the heart, the
gastrointestinal and endocrine systems, and ultimately impairs
respiration. There are currently no approved treatment options,”
said João Siffert, M.D., president and chief executive officer of
Design Therapeutics. “Our DM1 GeneTACs are small molecules designed
to address the underlying root causes of DM1 by specifically
blocking transcription of the mutant DMPK gene.”
“New preclinical data demonstrated the ability of our DM1
GeneTACs to potently and selectively block expression of the mutant
DMPK gene in DM1 patient cells. Reduction of nuclear foci was
associated with clear correction of splicing defects that are
involved in the multi-system pathophysiology of DM1,” added Abhi
Bhat, Ph.D., head of R&D of Design Therapeutics. “We believe
these data are highly meaningful both for the potential treatment
of patients with DM1, as well as further validation of our GeneTAC
approach to treating inherited degenerative diseases.”
Design is leveraging its proprietary GeneTAC (gene targeted
chimera) platform to develop therapeutic candidates for inherited
diseases driven by nucleotide repeat expansions, such as DM1. DM1
is caused by an increased number of CTG triplet repeats in the DMPK
gene. Transcription of the mutant DMPK gene forms pre-mRNAs with
large CUG hairpin loops that trap splicing proteins in the nucleus.
Specifically, the mutant DMPK pre-mRNAs trap a critical CUG-binding
protein called muscle blind-like protein 1 (MBNL1), which leads to
the formation of toxic nuclear foci. These foci inhibit the ability
of MBNL1 to process pre-mRNAs, which when mis-spliced disrupt
muscle development and function that is characteristic of DM1.
Design’s DM1 GeneTAC program is designed to block transcription
of the mutant DMPK gene and prevent the formation of the CUG
hairpin structures that trap MBNL1, thereby addressing the
underlying cause of the disease. New preclinical data being
presented from studies of Design’s DM1 GeneTAC showed:
- near-complete resolution of toxic nuclear foci of greater than
90% in DM1 patient fibroblasts and myoblasts, with dose-responsive
resolution at concentrations less than 100 nM;
- near-complete correction of splicing defects in the MBNL1 gene
of greater than 90% in DM1 patient myoblasts, also at
concentrations less than 100 nM;
- highly selective knockdown of the mutant DMPK allele without
affecting the normal, wild-type allele following a 72-hour
treatment period in patient fibroblasts;
- resolution of CUG foci at substantially greater levels than
with antisense oligonucleotide controls in both primary myotubes
and primary myoblast patient cells;
- redistribution of MBNL1 from aggregates in DM1 patient-derived
myotubes; and
- biodistribution to key tissues implicated in DM1, skeletal
muscle and heart, at concentrations above those needed to reverse
splicing defects in vitro at doses that were well-tolerated in
rodents.
These data, supplemented by a growing body of data from the
company’s GeneTAC program for Friedrich ataxia, support the
continued advancement of the DM1 program and rationale to evaluate
the utility of the GeneTAC approach in multiple additional
nucleotide repeat expansion diseases.
About Design TherapeuticsDesign Therapeutics,
Inc. (Nasdaq: DSGN) is a biotechnology company developing a new
class of therapies based on a platform of gene targeted chimera
(GeneTAC™) small molecules. The company’s GeneTAC molecules are
designed to either turn on or turn off a specific disease-causing
gene to address the underlying cause of disease. Design’s lead
program is focused on the treatment of Friedreich ataxia, followed
by a program in myotonic dystrophy type-1 and discovery efforts for
multiple other serious degenerative disorders caused by nucleotide
repeat expansions. For more information, please visit
designtx.com.
Forward Looking StatementsStatements in this
press release that are not purely historical in nature are
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements include,
but are not limited to, statements related to: preclinical data and
the relevance of such data; Design’s DM1 GeneTAC program and its
design and potential therapeutic benefits and advantages; and
Design’s GeneTAC approach. Because such statements are subject to
risks and uncertainties, actual results may differ materially from
those expressed or implied by such forward-looking statements.
Words such as "believes," “designed to,” "anticipates," "plans,"
"expects," "intends," "will," "goal," "potential" and similar
expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon Design’s current
expectations and involve assumptions that may never materialize or
may prove to be incorrect. Actual results and the timing of events
could differ materially from those anticipated in such
forward-looking statements as a result of various risks and
uncertainties, which include, without limitation, risks associated
with the process of discovering, developing and commercializing
therapies that are safe and effective for use as human therapeutics
and operating as a development stage company; Design’s ability to
develop, initiate or complete preclinical studies and clinical
trials for, obtain approvals for and commercialize any of its
product candidates; the risk that promising early research or
clinical trials do not demonstrate safety and/or efficacy in later
preclinical studies or clinical trials; changes in Design’s plans
to develop and commercialize its product candidates; the risk that
Design may not obtain approval to market its product candidates;
uncertainties associated with performing clinical trials,
regulatory filings and applications; risks associated with reliance
on third parties to successfully conduct clinical trials and
preclinical studies; changes in Design’s plans to develop and
commercialize its product candidates; Design’s ability to raise any
additional funding it will need to continue to pursue its business
and product development plans; regulatory developments in the
United States and foreign countries; Design’s reliance on key third
parties, including contract manufacturers and contract research
organizations; Design’s ability to obtain and maintain intellectual
property protection for its product candidates; our ability to
recruit and retain key scientific or management personnel;
competition in the industry in which Design operates; and market
conditions. For a more detailed discussion of these and other
factors, please refer to Design’s filings with the Securities and
Exchange Commission (“SEC”), including under the “Risk Factors”
heading of Design’s Quarterly Report on Form 10-Q for the quarter
ended June 30, 2021, as filed with the SEC on August 9, 2021. You
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof. All
forward-looking statements are qualified in their entirety by this
cautionary statement and Design undertakes no obligation to revise
or update this press release to reflect events or circumstances
after the date hereof, except as required by law.
Contact: Chelcie ListerTHRUST Strategic
Communications(910) 777-3049chelcie@thrustsc.com
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