Passage Bio Highlights University of Pennsylvania’s Gene Therapy Program’s Newly Published Research to Prevent Toxicity Associated with Gene Therapy

PHILADELPHIA, Nov. 11, 2020 (GLOBE NEWSWIRE) — Passage Bio, Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system (CNS) disorders, today commends the newly published research of the University of Pennsylvania’s (Penn) Gene Therapy Program (GTP) regarding a novel targeted approach to prevent a selective neurotoxicity seen in the sensory neurons of dorsal root ganglia (DRG) after gene therapy treatment. As previously published, this DRG toxicity has been observed after both systemic and central nervous system (CNS) delivery of gene therapy and across a variety of vectors in pre-clinical models, but clinical manifestations have not been observed.¹
As part of its unique collaboration agreement with Penn, Passage Bio has certain rights to this novel DRG technology for the indications the company progresses with Penn.“Although our safety studies for our programs have not shown any clinical manifestations of DRG toxicity, we are excited about the promising approach developed by Penn’s GTP,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “As part of our mission to develop transformative therapies for patients, we remain committed to advancing the field of gene therapy. If in the future this new approach shows clinical benefit for patients, we will be in a strong position to incorporate it into our programs. Our relationship with Penn’s GTP is an important distinguishing characteristic of Passage Bio. Through our collaboration, we have ready access to world-class expertise and groundbreaking research that we can rapidly apply, if appropriate, to our therapeutic programs.”GTP’s research on preventing DRG toxicity published online this week in Science Translational Medicine. According to the researchers, DRG toxicity is the result of over expression of an introduced gene, known as a transgene, in cells in the DRG, a cluster of neural cells on the outside of the spinal cord responsible for transmission of sensory messages. To correct this over expression, the GTP research team modified a transgene with a microRNA target designed to reduce the level of the transgene expression in DRG neurons as well as toxicity in DRG neurons, without affecting transduction elsewhere in the brain. That alteration eliminated more than 80 percent of the transgene expression in DRG neurons and reduced the related DRG toxicity in preclinical studies with primates.James M. Wilson, M.D., Ph.D., director of Penn’s GTP and a chief scientific advisor at Passage Bio, served as a senior author of the published manuscript. Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penn’s GTP is first author. They reported that their microRNA target approach may be a straightforward way to potentially make AAV therapy for the central nervous system more safe.As previously reported, results from preclinical toxicology studies for Passage Bio’s lead therapeutic programs, PBGM01 (GM1 gangliosidosis), PBKR03 (Krabbe disease), PBFT02 (FTD-GRN), were consistent with this overall AAV platform observation, and showed no clinical manifestations in detailed neurological examinations or daily observations. To proactively determine whether there is appearance of clinical signs of DRG toxicity in our clinical programs, Passage Bio will implement monitoring of patients, consisting of both nerve-conduction studies and neurological exams focused on sensory and peripheral nerve functions.Passage Bio is advancing six programs, which include the lead programs for GM1 gangliosidosis (GM1), Krabbe disease, and frontotemporal dementia (FTD), as well as three additional programs for amyotrophic lateral sclerosis (ALS), metachromatic leukodystrophy (MLD) and Charcot-Marie-Tooth disease Type 2a (CMT2a). The company anticipates that the initial three clinical candidates will be in clinical trials in 2021. Through its collaboration agreement with Penn, Passage Bio has the option to license a total of 17 programs focused on rare, monogenic disorders of the CNS.About Passage BioAt Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic 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 unparalleled 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 www.passagebio.com.Penn Financial DisclosureDr. Wilson is a Penn faculty member and also a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the Company, receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, he may receive additional financial benefits under the license in the future. The University of Pennsylvania also holds equity and licensing interests in Passage Bio.Forward-Looking StatementsFor further information, please contact:Investors:
Sarah McCabe and Zofia Mita
Stern Investor Relations, Inc.
212-362-1200
sarah.mccabe@sternir.com
Zofia.mita@sternir.comMedia:
Gwen Fisher
Passage Bio
215-407-1548
gfisher@passagebio.com¹ Juliette Hordeaux, Elizabeth L. Buza, et al. “Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology,” Human Gene Therapy, published online June 25, 2020.