• Preclinical studies conducted with University of Pennsylvania’s Gene Therapy Program demonstrate biologic effects of vector-optimized gene therapy PBKR03 for Krabbe disease
  • PBKR03 showed marked improvements in safety, disease progression and key biomarkers for Krabbe disease in large and small animal models
  • Company is enrolling patients for cohort 1 in global clinical trial, GALax-C, with PBKR03 for infantile Krabbe disease, a rare, fatal pediatric condition
PHILADELPHIA, March 29, 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 publication of the robust pre-clinical studies that supported clinical study initiation for PBKR03 gene therapy for infantile Krabbe disease. In the paper reporting these preclinical results, Juliette Hordeaux, D.V.M., Ph.D., D.E.C.V.P., and colleagues from University of Pennsylvania’s Gene Therapy Program (GTP), report marked improvements in both disease progression and key biomarkers in large and small animal models of Krabbe disease following a single administration of PBKR03, with no observed dose-limiting toxicities. The paper is published online ahead of print in the May issue of Human Gene Therapy.
Krabbe disease is a rare pediatric lysosomal storage disorder caused by mutations in the GALC gene, which encodes galactosylceramidase, an enzyme that breaks down galactosylceramide and psychosine. Without adequate levels of galactosylceramidase, psychosine accumulates, causing widespread death of myelin-producing cells and progressive damage to neurons in both the brain and peripheral tissues of affected children. This is characterized in children by loss of acquired milestones, staring episodes, apnea, peripheral neuropathy, severe weakness, unresponsiveness to stimuli, seizures, blindness, and deafness. Life expectancy for infantile Krabbe disease, the most severe form, is two years.
“The benefits of our strategic collaboration with GTP are apparent when you see the robust preclinical data underpinning our decision to move forward with PBKR03 for infantile Krabbe disease,” said Bruce Goldsmith, Ph.D., chief executive officer and president, Passage Bio. “These preclinical studies support our belief that gene replacement with PBKR03 has the potential to provide meaningful clinical benefit by reducing neuronal demyelination and damage to both the central and peripheral nervous systems of children with infantile Krabbe disease. As previously announced, the first child with infantile Krabbe disease has now received PBKR03 in Passage Bio’s clinical study – GALax-C – and we look forward to continued enrollment in the initial cohort.”
For the preclinical studies, the researchers selected animal models in which a spontaneous mutation in the GALC gene recapitulates certain characteristics of human disease in the animal’s central and peripheral nervous systems, such as low or no GALC enzyme activity, toxic accumulation of psychosine, and rapid neurological deterioration. Their experiment in mice which was designed to approximate developmental age and disease stage of the intended population with infantile Krabbe disease showed that administration of PBKR03 into the cerebrospinal fluid (CSF) led to dose-dependent improvements in histopathological, biochemical, and clinical disease signs.
Further, in a canine model of Krabbe disease, intra-cisterna magna (ICM) delivery of the AAV gene therapy resulted in elevated GALC enzyme activity in brain, spinal cord and CSF, reduced psychosine accumulation, and preserved central and peripheral nerve myelination compared to the control group. This led to marked improvements in nerve conduction function, ambulation, and survival. In Passage Bio’s clinical trial GALax-C, patients are also administered PBKR03 via ICM.
James Wilson, M.D., Ph.D., director of the Gene Therapy Program (GTP); Rose H. Weiss professor and director, Orphan Disease Center; professor of Medicine and Pediatrics, Perelman School of Medicine at the University of Pennsylvania; and chief scientific advisor of Passage Bio, said: “Krabbe disease is well understood as a therapeutic target and this allowed our team to take a very thoughtful approach when selecting a vector and route of administration for our preclinical studies, optimizing for transduction. By selecting an AAVhu68 vector and route of administration that delivers a functional GALC gene to the affected systems, we have shown remarkable effects across these animal models, including normalization of nerve function in the canine study. These results were also achieved without bone marrow transplantation or immune suppression.”
This research was supported by a Research, Collaboration and License Agreement with Passage Bio. Human Gene Therapy is the official journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies. Click here to read the full-text article
About PBKR03
PBKR03 utilizes a next-generation proprietary AAV capsid to deliver, through ICM administration, a functional GALC gene into the CSF. The GALax-C Phase I/II study utilizing PBKR03 is currently enrolling the first cohort of patients with infantile Krabbe disease with mutations in the gene that codes for galactosylceramidase. The gene therapy has the potential to treat both the central nervous system and peripheral nerve manifestations observed in patients with Krabbe disease.
The U.S. Food and Drug Administration (FDA) has granted PBKR03 Fast Track, Orphan Drug, and Rare Pediatric Disease designations. PBKR03 has also received an Orphan designation from the European Commission.
About Passage Bio
At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming genetic medicines for patients with CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. 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. This provides our team with 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 into clinical testing. 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
Penn Financial Disclosure
Dr. Wilson is a Penn faculty member as well as a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the company, his laboratory at Penn receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, Dr. Wilson may receive additional financial benefits in the future. The University of Pennsylvania receives sponsored research funding from Passage Bio and has licensed intellectual property to the company that may result in future financial returns to Penn.
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 subsequent events in our GALax-C trial; 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; our expectations about manufacturing plans and strategies; and the ability of our lead product candidates to treat their respective target 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.
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