Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic
medicines company focused on improving the lives of patients with
neurodegenerative diseases, today announced initial safety and
biomarker data from three Cohort 1 patients in the ongoing global
Phase 1/2 upliFT-D clinical trial evaluating PBFT02, an
adeno-associated virus (AAV)-delivery gene therapy for the
treatment of patients with frontotemporal dementia (FTD) with
granulin (GRN) mutations. FTD is a form of early onset dementia
with no approved disease-modifying therapies. Additionally, the
company shared updated strategic priorities aimed at further
optimizing its portfolio for the treatment of neurodegenerative
conditions.
"We are proud to announce initial clinical data from our
upliFT-D clinical trial, which showcases the ability of PBFT02 to
elevate CSF progranulin to supraphysiologic levels at the lowest
tested dose, Dose 1, up to six months post-treatment. We believe
these data, surpassing our expectations based on preclinical
non-human primate models, validate the compelling potential of
PBFT02 to address progranulin deficiency—a key driver of disease
progression in individuals with FTD-GRN,” said Mark Forman, M.D.,
Ph.D., chief medical officer at Passage Bio.
FTD is one of the more common causes of early-onset dementia. In
approximately 5 to 10 percent of individuals with FTD–approximately
18,000 individuals in the United States and Europe—the disease
occurs because of mutations in the GRN gene, causing a deficiency
of progranulin (PGRN). PGRN is a complex and highly conserved
protein thought to have multiple roles in cell biology, development
and inflammation. Emerging evidence suggests that PGRN deficiency
may contribute to lysosomal dysfunction.
The upliFT-D clinical trial evaluates PBFT02 as a single dose
delivered via intra-cisterna magna (ICM) injection. PBFT02 uses an
AAV1 viral vector to deliver a functional copy of the GRN gene
encoding PGRN to a patient's cells.
Topline interim results from first three patients in the
uplift-D clinical trial
Safety (patient follow-up up to six months)
- Dose 1 of PBFT02 was generally well-tolerated in patients 2 and
3, who received an enhanced steroid regimen following protocol
amendment.
- No serious adverse events (SAEs).
- All treatment emergent adverse events (AEs) were mild to
moderate in severity.
- No evidence of clinically significant immune response,
hepatotoxicity or safety related imaging abnormalities.
- Patient 1 received a low level of immunosuppression (60 mg oral
prednisone for 60 days) and experienced two SAEs that were both
asymptomatic and consistent with an immune response.
- Following patient 1, the protocol was amended to increase the
steroid regimen (1,000 mg IV methylprednisolone on days 1-3
followed by 60 mg oral prednisone through day 60) for patients 2
and 3.
- No evidence of dorsal root ganglion (DRG) toxicity, as measured
by nerve conduction studies, and no complications were observed
related to ICM administration across any of the three
patients.
Biomarkers
- Dose 1 of PBFT02 treatment resulted in a 3.6 to 6.6-fold
increase in CSF PGRN at day 30 (n=3) relative to baseline. CSF PGRN
increased to supraphysiologic levels of 10.7 to 17.3 ng/mL at day
30, exceeding the range found in healthy adult controls of 3.3 to
8.2 ng/mL (n=61).
- CSF PGRN remained at supraphysiologic levels at six months with
a concentration of 27.3 ng/mL (n=1).
- Plasma PGRN levels remained below levels found in healthy adult
controls through the available follow-up period across all
patients.
"Driven by promising initial data for PBFT02 in FTD-GRN and
evidence supporting progranulin’s role in neurodegeneration, we are
refining our strategic priorities to explore the therapeutic
potential of PBFT02 in multiple diseases, including FTD-C9orf72,
amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease,” said
William Chou, M.D., president and chief executive officer at
Passage Bio. “As we pursue this strategy, we are actively exploring
potential partnerships to advance our GM1 gangliosidosis program as
well as our other clinical-stage pediatric programs. This shift in
strategy aims to optimize focus and resources and provides each of
our gene therapy candidates the best chance to get to patients in
need.”
Strategic Priorities
We are focused on the following key strategic priorities:
- Continuing clinical development of PBFT02 to treat
FTD-GRN.
- Pursuing PBFT02 in additional adult neurodegenerative diseases,
including FTD-C9orf72, ALS and Alzheimer’s disease.
- Prioritizing Huntington’s disease preclinical program through
existing Penn Gene Therapy Program partnership.
- Pursuing potential partnership opportunities for clinical-stage
pediatric programs in GM1 gangliosidosis, Krabbe disease and
metachromatic leukodystrophy (MLD).
Anticipated Upcoming Milestones
FTD-GRN
- Initiate dosing for Cohort 2 FTD-GRN patients in 1H 2024
- Report full 6-month safety and biomarker data from Cohort 1
patients in 2H 2024
- Report 12-month follow-up data from Cohort 1 patients in 1H
2025
- Report initial safety and biomarker data from Cohort 2 patients
in 1H 2025
FTD-C9orf72 and ALS
- Obtain regulatory feedback on the pathway to treating
FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024
These strategic priorities and clinical milestones underscore
Passage Bio's dedication to advancing cutting-edge, one-time
genetic medicines and protecting patients and families against loss
in neurodegenerative conditions.
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 upliFT-D (NCT04747431)
upliFT-D is a Phase 1/2 global, multi-center, open-label,
dose-escalation clinical trial of PBFT02 administered by single
injection into the cisterna magna in patients aged 35 to 75 years
with FTD-GRN.
The upliFT-D clinical trial will investigate two dose levels of
PBFT02. The clinical trial will sequentially enroll two cohorts,
with an optional third dose level cohort expected to be enrolled
based on the results of the first two cohorts. Enrollment is
currently ongoing. The primary endpoint of the clinical trial is to
evaluate the safety and tolerability of PBFT02. Secondary endpoints
include disease biomarkers and clinical outcome measures. upliFT-D
is a two-year clinical trial with a three-year safety extension.
Passage Bio is pursuing several initiatives to support clinical
trial recruitment and enrollment, including a collaborative
partnership with InformedDNA to provide no-cost genetic counseling
and testing for adults who have been diagnosed by their physicians
with FTD. More information about upliFT-D can be found
here.
About PBFT02
PBFT02 utilizes an AAV1 viral vector to deliver, through ICM
administration, a functional GRN gene to patients with mutations in
the gene that encodes for progranulin (PGRN). This vector and
delivery approach aims to provide higher-than-normal levels of the
PGRN protein to the CNS to overcome the progranulin deficiency in
GRN gene mutation carriers.
PBFT02 is supported by extensive preclinical studies conducted
by Passage Bio’s collaborator, the University of Pennsylvania’s
Gene Therapy Program. The studies showed compelling evidence
indicating broad transduction across the brain, including high
transduction of ependymal cells, and demonstrated robust increases
in cerebrospinal fluid (CSF) PGRN concentrations.
About Passage Bio
Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines
company on a mission to improve the lives of patients with
neurodegenerative diseases. Our primary focus is the development
and advancement of cutting-edge, one-time therapies designed to
target the underlying pathology of these conditions. Passage Bio’s
lead product candidate, PBFT02, seeks to treat neurodegenerative
conditions, including frontotemporal dementia, by elevating
progranulin levels to restore lysosomal function and slow disease
progression.
To learn more about Passage Bio and our steadfast commitment to
protecting patients and families against loss in neurodegenerative
conditions, please visit: www.passagebio.com.
Forward-Looking StatementsThis 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 the progress of clinical trials
and the availability of clinical data from such trials; our
expectations about our collaborators’ and partners’ ability to
execute key initiatives; our expectations about manufacturing plans
and strategies; our expectations about cash runway; our
expectations about potential partnerships related to PBGM01, PBKR03
and PBML04 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; 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:Madeline Nafus Passage Bio 910.401.7283
mnafus@passagebio.com
Media:Mike BeyerSam Brown Inc. Healthcare
Communications312.961.2502MikeBeyer@sambrown.com
Passage Bio (NASDAQ:PASG)
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から 6 2023 まで 6 2024