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Passage Bio Doses First Patient in Global Clinical Trial of PBFT02 Gene Therapy for Frontotemporal Dementia with Granulin Mutations

August 11, 2022

PHILADELPHIA, Aug. 11, 2022 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders, today announced that the first patient has been dosed in the 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.

“Dosing the first patient in our upliFT-D trial is an important milestone for the Passage Bio team and for the PBFT02 program, our first program in the clinic for adults,” said Edgar (Chip) Cale, interim chief executive officer of Passage Bio. “We look forward to continuing our important work to develop PBFT02 as a potential treatment option for the thousands of people living with FTD-GRN. We are grateful for the support from the families and clinical trial investigators who have chosen to participate in our studies.”

The upliFT-D clinical study evaluates PBFT02 as a single dose delivered via intra-cisterna magna (ICM) injection. This gene therapy uses an AAV1 viral vector to deliver a functional copy of the GRN gene encoding progranulin (PGRN) to a patient's cells. 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.

“FTD-GRN is a devastating disease with no approved disease-modifying therapies, and we are hopeful this trial will provide evidence that PBFT02 could become a meaningful treatment option for adults living with FTD-GRN,” said Mark Forman, M.D., Ph.D., chief medical officer of Passage Bio. “Our approach, which employs the AAV1 vector and ICM administration, provides a potential opportunity to achieve higher than normal levels of PGRN in the CNS, thereby overcoming the PGRN deficiency in GRN mutation carriers with a diagnosis of early symptomatic FTD-GRN. We look forward to building on our preclinical data with this Phase 1/2 trial.”

FTD is one of the more common causes of early-onset dementia. In approximately 5 to 10 percent of individuals with FTD–3,000 to 6,000 individuals in the United States–the disease occurs because of mutations in the GRN gene, causing a deficiency of PGRN. FTD causes impairment in behavior, language and executive function, as well as changes in personal and social conduct including loss of inhibition, apathy, and social withdrawal. Progression of FTD results in an average survival of eight years after the onset of symptoms.

The U.S. Food and Drug Administration (FDA) has granted PBFT02 Fast Track and Orphan Drug designations. PBFT02 has also received an Orphan designation from the European Commission.

upliFT-D continues to enroll patients with early symptomatic FTD-GRN. If you are interested in a referral to a clinical trial site, please contact Passage Bio here to learn more.

About upliFT-D (NCT04747431)

upliFT-D is a Phase 1/2 global, multi-center, open-label, dose-escalation study of PBFT02 administered by single injection into the cisterna magna in patients aged 35 to 75 years with early symptomatic FTD-GRN.

The upliFT-D study will investigate two dose levels of PBFT02. The study 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 study is to evaluate the safety and tolerability of PBFT02. Secondary endpoints include disease biomarkers and clinical outcome measures. upliFT-D is a two-year study 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. To date, upliFT-D has received CTA acceptance in the United States, Canada and Brazil. 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, including broad transduction across the brain, including high transduction of ependymal cells, and demonstrated increases in cerebrospinal fluid (CSF) PGRN concentrations to >50-fold normal human CSF PGRN concentrations.

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 three clinical programs in GM1 gangliosidosis, Krabbe disease, and frontotemporal dementia with several additional programs in preclinical development. 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

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 future milestones related to our PBFT02 program; timing and execution of anticipated trial designs and milestones, including initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; 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:

Passage Bio Investors:

Stuart Henderson
Passage Bio

Passage Bio Media:
Mike Beyer
Sam Brown Inc. Healthcare Communications


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