Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic
medicines company focused on developing transformative therapies
for central nervous system (CNS) disorders, today announced new
interim safety, biomarker, and survival data from cohorts 1-4 in
the Imagine-1 clinical study. Imagine-1 is a Phase 1/2, global,
open-label, dose-escalation study of the AAVhu68 gene therapy
PBGM01 delivered by intra-cisterna magna (ICM) injection in six
cohorts of pediatric subjects with early and late infantile GM1
Gangliosidosis (GM1). GM1 is a rare, fatal lysosomal storage
disease in which mutations in the GLB1 gene result in very low
activity of the enzyme beta-galactosidase (β-Gal).
"We are highly encouraged by the compelling data emerging from
our Imagine-1 study, with results underscoring the potential of
PBGM01 to be a transformative therapy for GM1 patients,” said
William Chou, M.D., president and chief executive officer of
Passage Bio. “Updated data from the first eight treated patients
show that PGBM01 continues to have a favorable safety profile, is
well tolerated and shows initial evidence of improved survival
relative to what is predicted by the natural history of the
disease. Furthermore, Dose 2 of PBGM01 has shown the ability to
achieve healthy control levels of β-Gal activity and GM1
gangliosides in CSF, with durability up to 12 months after
treatment.”
“Our momentum in the Imagine-1 study continues to be strong as
the program progresses to evaluate its highest dose level, Dose 3,
in patients with early and late infantile GM1,” Dr. Chou continued.
“We are excited to share that we have treated the first patient at
Dose 3, and we are actively recruiting additional patients at
clinical trial sites across multiple countries. We look forward to
sharing initial data from Dose 3 patients by mid-2024 and want to
express our deepest gratitude for the dedication and collaboration
demonstrated by the families and investigators who have
participated in our Imagine-1 trial.”
Topline interim results from cohorts 1-4 of the
Imagine-1 study
Safety (patient follow-up ranged from 8 to 28
months)
- No treatment-related serious adverse events (SAEs)
- All treatment-related adverse events (AEs) were mild to
moderate in severity
- No clinically significant changes in liver function requiring
intervention
- No evidence of dorsal root ganglion (DRG) toxicity in nerve
conduction studies
- No complications related to ICM administration
- Favorable immunological profile with no clinically significant
immune response
Survival
- Imagine-1 study patients showed
initial evidence of improved survival relative to natural history
data
- Natural history data from a
meta-analysis of 154 GM1 infants with symptom onset <12 months
of age indicates mean survival for infantile GM1 of 18.9 months and
no survival beyond 35 monthsi
- Infantile GM1 patients receiving
PBGM01 showed a survival benefit, with one hundred percent survival
beyond 20 months of age (n=3)
Biomarkers
- Dose 2 of PBGM01 resulted in
robust and durable increases in CSF β-Gal activity
- In 3 of 4 children, Dose 2 of
PBGM01 resulted in a 4.7-16.1x increase in CSF β-Gal activity at 30
days post-treatment relative to baseline, exceeding average levels
seen in healthy adults and GM1 Natural History Study (NHSii)
- Increased CSF β-Gal activity was
able to be sustained for up to 12 months
- Dose 2 of PBGM01 decreased CSF GM1
ganglioside levels and demonstrated the ability to achieve normal
adult levels at one-year post-dose
- GM1 ganglioside levels continued
to decline over time in all patients treated with Dose 2
- Effects on CSF β-Gal activity and
GM1 gangliosides were dose-dependent, with Dose 1 of PBGM01
exhibiting modest effects
The company has treated the first patient at Dose 3 and is
actively recruiting additional patients in the Imagine-1 study for
Cohort 5 (late infantile) and Cohort 6 (early infantile). The
amended study protocol has been approved at several clinical trial
sites, including in Brazil, Canada, Turkey and the United States.
Dosing of patients in Cohorts 5 and 6 may occur concurrently, and
the company expects to report initial safety and biomarker data
from Dose 3 by mid-2024.
Conference Call Details
Passage Bio will host a conference call and webcast today at
8:30 a.m. ET. To register for the event, please use the following
link. A live audio webcast of the event will be available on the
Investors & News section of Passage Bio’s website at
investors.passagebio.com. The archived webcast will be available on
Passage Bio's website approximately two hours after the completion
of the event and for 30 days following the call.
About Imagine-1
Imagine-1 is a Phase 1/2, global, open-label, dose-escalation
study of PBGM01 administered by a single injection into the
cisterna magna in pediatric subjects with early and late infantile
GM1. The clinical program consists of six patient cohorts, with
separate dose-escalation cohorts for late infantile GM1 and early
infantile GM1. The primary goal of the study is to first assess
safety and tolerability and then efficacy of PBGM01 in patients.
The U.S. Food and Drug Administration (FDA) has granted PBGM01 Fast
Track, Orphan Drug, and Rare Pediatric Disease designations. PBGM01
has also received an Orphan designation from the European
Commission.
To learn more about the clinical trial program, please visit
ClinicalTrials.gov: NCT04713475.
About PBGM01
PBGM01 is an AAV-delivery gene therapy currently being developed
for the treatment of infantile GM1, in which patients have
mutations in the GLB1 gene causing little or no residual
beta-galactosidase enzyme activity and subsequent
neurodegeneration. PBGM01 utilizes a next-generation AAVhu68 capsid
administered through the cisterna magna to deliver a functional
GLB1 gene encoding beta-galactosidase to the brain and peripheral
tissues. By increasing beta-galactosidase activity, PBGM01 has the
potential to reduce accumulation of toxic GM1 gangliosides and
reverse neuronal toxicity, thereby restoring developmental
potential. In preclinical models, PBGM01 has demonstrated broad
brain distribution and high levels of expression of the
beta-galactosidase enzyme in both the CNS and critical peripheral
organs, suggesting potential treatment for both the CNS and
peripheral manifestations of GM1.
About GM1
GM1, a rare monogenic lysosomal storage disease, is caused by
mutations in the GLB1 gene, which encodes the lysosomal enzyme
beta-galactosidase (β-gal). Reduced β-gal activity results in the
accumulation of toxic levels of GM1 gangliosides in neurons
throughout the brain, causing rapidly progressive
neurodegeneration. GM1 accumulation also results in progressive
damage to other tissues including the heart, liver, and bones and
manifests with hypotonia (reduced muscle tone), progressive CNS
dysfunction, seizures, and rapid developmental regression. Life
expectancy for infants with GM1 ranges from 2-10 years, and
infantile GM1 represents approximately 60 percent of the global GM1
incidence of 0.5 to 1 in 100,000 live births.
About Passage Bio
Passage Bio (Nasdaq: PASG) is a clinical-stage genetic medicines
company on a mission to provide life-transforming therapies for
patients with CNS diseases with limited or no approved treatment
options. Our portfolio spans pediatric and adult CNS indications,
and we are currently advancing clinical programs in GM1
gangliosidosis and frontotemporal dementia and our preclinical
pipeline, including programs in amyotrophic lateral sclerosis and
Huntington’s disease. Based in Philadelphia, PA, our company has
established a strategic collaboration and licensing agreement with
the renowned University of Pennsylvania’s Gene Therapy Program to
conduct our discovery and IND-enabling preclinical work. Through
this collaboration, we have enhanced access to a broad portfolio of
gene therapy candidates and future gene therapy innovations that we
then pair with our deep clinical, regulatory, manufacturing and
commercial expertise to rapidly advance our robust pipeline of
optimized gene therapies. As we work with speed and tenacity, we
are always mindful of patients who may be able to benefit from our
therapies. More information is available
at www.passagebio.com.
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of, and made pursuant to the safe harbor provisions of,
the Private Securities Litigation Reform Act of 1995, including,
but not limited to: our expectations about timing and execution of
anticipated milestones, including progress of the Imagine-1
clinical trial and the availability of clinical data from the
trial; our expectations about our collaborators’ and partners’
ability to execute key initiatives; our expectations about
manufacturing plans and strategies; our expectations about cash
runway; and the ability of our lead product candidates to treat
their respective target monogenic CNS disorders. These
forward-looking statements may be accompanied by such words as
“aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,”
“forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,”
“possible,” “will,” “would,” and other words and terms of similar
meaning. These statements involve risks and uncertainties that
could cause actual results to differ materially from those
reflected in such statements, including: our ability to develop and
obtain regulatory approval for our product candidates; the timing
and results of preclinical studies and clinical trials; risks
associated with clinical trials, including our ability to
adequately manage clinical activities, unexpected concerns that may
arise from additional data or analysis obtained during clinical
trials, regulatory authorities may require additional information
or further studies, or may fail to approve or may delay approval of
our drug candidates; the occurrence of adverse safety events; the
risk that positive results in a preclinical study or clinical trial
may not be replicated in subsequent trials or success in early
stage clinical trials may not be predictive of results in later
stage clinical trials; failure to protect and enforce our
intellectual property, and other proprietary rights; our dependence
on collaborators and other third parties for the development and
manufacture of product candidates and other aspects of our
business, which are outside of our full control; risks associated
with current and potential delays, work stoppages, or supply chain
disruptions caused by the coronavirus pandemic; and the other risks
and uncertainties that are described in the Risk Factors section in
documents the company files from time to time with the Securities
and Exchange Commission (SEC), and other reports as filed with the
SEC. Passage Bio undertakes no obligation to publicly update any
forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information,
future developments or otherwise.
For further information, please contact:
Investors: Stuart Henderson Passage Bio
267.866.0114 shenderson@passagebio.com
Media:Mike BeyerSam Brown Inc. Healthcare
Communications312.961.2502MikeBeyer@sambrown.com
i Lang, F. M., Korner, P., Harnett, M., Karunakara, A., &
Tifft, C. J. (2020). The natural history of Type 1 infantile GM1
gangliosidosis: A literature-based meta-analysis. Molecular
genetics and metabolism, 129(3), 228-235.ii Based on
preliminary data from University of Pennsylvania’s ODC Natural
History Study (NHS) (NCT04041102); value range (0.3-1.81
nmol/mL/3hr)
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