– Significant mean splicing correction of 29.1%
following a single dose of PGN-EDODM1 at 10 mg/kg –
– PGN-EDODM1 observed to have favorable
emerging safety profile –
– Conference call scheduled today at 8:00 a.m.
ET –
PepGen Inc. (Nasdaq: PEPG), a clinical-stage biotechnology
company advancing the next generation of oligonucleotide therapies
with the goal of transforming the treatment of severe neuromuscular
and neurological diseases, today announced initial positive
clinical data from the 5 and 10 mg/kg dose cohorts in the ongoing
FREEDOM-DM1 Phase 1 trial investigating PGN-EDODM1 in myotonic
dystrophy type 1 (DM1).
“These results far exceeded our expectations for splicing
correction following a single dose of PGN-EDODM1. Mis-splicing is
the underlying cause of DM1 pathology, and we believe the mean
splicing correction observed at 28 days following a single dose of
PGN-EDODM1 at 10 mg/kg in the FREEDOM clinical trial surpasses
those reported to date in multi-dose clinical trials of up to nine
months in duration in patients with DM1. We believe this is a
strong indicator of our EDO technology’s potential to deliver
therapeutic oligonucleotides to the nucleus and PGN-EDODM1’s
potential to address the underlying cause of disease,” said James
McArthur, PhD, President and CEO of PepGen. “We believe these
results provide initial validation of PGN-EDODM1's ability to
selectively bind the pathogenic CUG-repeat DMPK RNA and we look
forward to evaluating PGN-EDODM1 with more doses over longer time
periods in our FREEDOM2-DM1 multiple ascending dose study. Based on
these initial results, we aim to build on the significant
correction of mis-splicing observed in this single-dose study to
potentially provide improved functional benefit for patients who
currently have no available approved therapeutic options.”
FREEDOM Results for the 5 mg/kg (n=8) and 10 mg/kg (n=8) Dose
Cohorts
Splicing, Muscle Tissue Concentration and Functional
Data:
- Mean splicing correction from evaluable participants was 12.3%
and 29.1% at 5 mg/kg (n=6) and at 10 mg/kg (n=4)1,2, respectively,
as measured by the 22-gene panel3 at 28 days post-dosing.
- Dose-dependent increase in muscle tissue concentrations of
PGN-EDODM1 was observed at 5 mg/kg (n=6) and at 10 mg/kg (n=5)1 at
day 28.
- While single-dose studies have not demonstrated improved
functional outcomes in DM1 patients, the Company collected data
from these cohorts and believes these data showed positive early
trends in some functional outcome measures. The Company believes
robust splicing correction with PGN-EDODM1 has the potential to
lead to meaningful functional improvements with repeat dosing over
time.
Safety and Tolerability Data:
- PGN-EDODM1 was observed to have a favorable emerging safety
profile in the 5 and 10 mg/kg cohorts through the data cut-off date
of December 3, 2024, which has continued through the date of this
release. There were no adverse events related to electrolytes or
renal biomarkers. Most of the treatment emergent adverse events
were mild or moderate in severity.
- There was one treatment-related serious adverse event of
abdominal pain in the 10 mg/kg cohort that was potentially
confounded by use of a prohibited, off-label drug taken on the
morning of PGN-EDODM1 dosing.
“These initial results from the FREEDOM clinical trial are
highly encouraging. The emerging safety profile is very promising.
The dose-dependent splicing correction may suggest that the drug
gets into the muscle and effectively binds to the target.
Mis-splicing is central to the cause of DM1, and correcting
mis-splicing may improve functional outcomes for DM1 patients over
time. With this in mind, I am particularly excited by the levels of
splicing correction seen after only a single dose of PGN-EDODM1.
Based on previous work, I believe that these effects could be
stronger as levels of the drug build up with repeat dosing,” said
Dr. Johanna Hamel, Associate Professor of Neurology, Pathology and
Laboratory Medicine at the University of Rochester Medical
Center.
The Company expects to report results from the FREEDOM 15 mg/kg
cohort in the second half of 2025 and from the FREEDOM2 5 mg/kg
cohort in the first quarter of 2026.
Conference Call Details
PepGen will host a conference call and webcast today at 8:00
a.m. ET to review the FREEDOM data. To access the call, please dial
(800) 218-2154 and provide the Conference ID 8807881. A live
webcast of the presentation will be available on the Events &
Presentations section of the PepGen investor website,
investors.pepgen.com.
About PGN-EDODM1
PGN-EDODM1, PepGen's investigational candidate in development
for the treatment of DM1, utilizes the Company's proprietary EDO
technology to deliver a therapeutic oligonucleotide that is
designed to restore the normal splicing function of MBNL1, a key
RNA splicing protein. PGN-EDODM1 is designed to directly address
the deleterious effects of cytosine-uracil-guanine (CUG) repeat
expansion in the dystrophia myotonica protein kinase (DMPK)
transcripts which sequester MBNL1, by binding to the pathogenic CUG
trinucleotide repeat expansion present in the DMPK transcripts,
disrupting the binding between the CUG repeat expansion and MBNL1.
We believe this mechanism will allow the DMPK transcripts to
continue performing their normal function within the cell, while
also liberating MBNL1 to correct downstream mis-splicing events. We
believe that this innovative therapeutic approach has considerable
advantages over oligonucleotide modalities that rely on knockdown
or degradation of the DMPK transcripts. The U.S. Food and Drug
Administration has granted PGN-EDODM1 both Orphan Drug and Fast
Track Designations for the treatment of patients with DM1.
About the FREEDOM Clinical Program
FREEDOM-DM1 is a multinational, randomized, double-blind,
placebo-controlled Phase 1 single ascending dose study, enrolling
up to approximately 32 adult participants with DM1 in multiple
geographies including the United States, the United Kingdom and
Canada, to evaluate the safety and tolerability of PGN-EDODM1. Per
the protocol, PGN-EDODM1 was administered at starting doses of 5
mg/kg and 10 mg/kg with subsequent dose escalation to 15 mg/kg, and
potentially in the future to 20 mg/kg, based upon evaluation by a
safety committee of safety data from the prior dose cohort(s).
Muscle biopsies are being conducted at baseline, at day 28 and at
week 16. In addition to safety and tolerability, oligonucleotide
muscle concentrations, splicing correction and functional outcome
measures are being assessed at day 28 and at week 16 following a
single dose of PGN-EDODM1.
FREEDOM2-DM1 is a Phase 2 randomized, double-blind,
placebo-controlled, multiple ascending dose clinical trial
evaluating PGN-EDODM1 in approximately 24 adult participants with
DM1 in Canada, the United Kingdom, and potentially other
geographies, including the United States, subject to regulatory
clearances.
About Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 is a monogenic, autosomal dominant,
progressive disorder that primarily affects skeletal, cardiac and
smooth muscles, with central nervous system symptoms also being
evident. Globally, the prevalence of DM1 is estimated to be 1 in
8,000 people, with approximately 40,000 patients in the United
States, 75,000 patients in Europe and 15,000 patients in Japan.
DM1 patients can suffer from various manifestations of disease
including myotonia, or a temporary rigidity due to the inability to
relax muscles, muscle weakness, cardiac abnormalities, respiratory
problems, fatigue, gastrointestinal complications, early cataracts,
and cognitive and behavioral impairments. For patients with more
severe forms of DM1, life expectancy is reduced due to increased
mortality rates resulting from pulmonary and cardiac
complications.
About PepGen
PepGen Inc. is a clinical-stage biotechnology company advancing
the next generation of oligonucleotide therapies with the goal of
transforming the treatment of severe neuromuscular and neurological
diseases. PepGen’s Enhanced Delivery Oligonucleotide (EDO) platform
is founded on over a decade of research and development and
leverages cell-penetrating peptides to improve the uptake and
activity of conjugated oligonucleotide therapeutics. Using these
EDO peptides, we are generating a pipeline of oligonucleotide
therapeutic candidates designed to target the root cause of serious
diseases.
For more information, please visit www.pepgen.com. Follow PepGen
on LinkedIn and X.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended. These statements may be identified by words such
as “aims,” “anticipates,” “believes,” “could,” “estimates,”
“expects,” “forecasts,” “goal,” “intends,” “may,” “plans,”
“possible,” “potential,” “seeks,” “will,” and variations of these
words or similar expressions that are intended to identify
forward-looking statements. Any such statements in this press
release that are not statements of historical fact may be deemed to
be forward-looking statements. These forward-looking statements
include, without limitation, statements regarding the therapeutic
potential and safety profile of PGN-EDODM1, including as it relates
to data from the 5 and 10 mg/kg cohorts of the FREEDOM-DM1 study,
the potential of our EDO platform to deliver higher levels of
oligonucleotide to the nuclei, our expectations regarding the
potential for significant correction of mis-splicing with more
doses of PGN-EDODM1 over a longer treatment period to potentially
provide improved functional benefit for patients with DM1, the
expected timing for additional data reports from our FREEDOM trial
and the initial data report from our FREEDOM2-DM1 trial, any
functional improvements that may result from robust splicing
correction with PGN-EDODM1, dose-dependent increases in splicing
suggesting that PGN-EDODM1 is getting into the muscle and
effectively binding to the target, and ongoing and planned
regulatory interactions.
Any forward-looking statements in this press release are based
on current expectations, estimates and projections only as of the
date of this release and are subject to a number of risks and
uncertainties that could cause actual results to differ materially
and adversely from those set forth in or implied by such
forward-looking statements. These risks and uncertainties include,
but are not limited to risks related to: delays or failure to
successfully initiate or complete our ongoing and planned
development activities for our product candidates, including
PGN-EDODM1; our ability to enroll patients in our clinical trials,
including FREEDOM and FREEDOM2; that our interpretation of clinical
and preclinical study results may be incorrect, or that we may not
observe the levels of therapeutic activity in clinical testing that
we anticipate based on prior clinical or preclinical results; our
product candidates, including PGN-EDODM1, may not be safe and
effective or otherwise demonstrate safety and efficacy in our
clinical trials; adverse outcomes from our regulatory interactions,
including delays in regulatory review, clearance to proceed or
approval by regulatory authorities with respect to our programs,
including clearance to commence planned clinical studies of our
product candidates, or other regulatory feedback requiring
modifications to our development programs, including in each case
with respect to our FREEDOM and FREEDOM2 programs; changes in
regulatory framework that are out of our control; unexpected
increases in the expenses associated with our development
activities or other events that adversely impact our financial
resources and cash runway; and our dependence on third parties for
some or all aspects of our product manufacturing, research and
preclinical and clinical testing. Additional risks concerning
PepGen’s programs and operations are described in our most recent
annual report on Form 10-K that is filed with the SEC. PepGen
explicitly disclaims any obligation to update any forward-looking
statements except to the extent required by law.
This release discusses PGN-EDODM1, an investigational therapy
that has not been approved for use in any country, and is not
intended to convey conclusions about its efficacy or safety. There
is no guarantee that PGN-EDODM1 or any other investigational
therapy will successfully complete clinical development or gain
regulatory authority approval.
- One participant’s biopsy was not collected at day 28 due to
pseudoaneurysm in connection with the biopsy procedure.
- One participant’s sample showed a splicing index outside the
pre-specified assay range at both baseline and day 28 (no
detectable mis-splicing) and was excluded from the analysis.
- Provenzano et al., The Splice Index as a prognostic biomarker
of strength and function in myotonic dystrophy type 1, J Clin.
Invest. 2025
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250224773471/en/
Investor Contact Dave Borah,
CFA SVP, Investor Relations and Corporate Communications
dborah@pepgen.com
Media Contact Julia Deutsch
Lyra Strategic Advisory Jdeutsch@lyraadvisory.com
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