Passage Bio Announces Publication of Preclinical Data That Show Single Injection of Optimized AAV Vector into Cerebral Spinal Fluid Corrects Neurological Disease, Supporting Advancement of PBGM01 into Clinic - Seite 2

Results of the PBGM01 preclinical study were reported in the paper titled, “A single injection of an optimized AAV vector into cerebrospinal fluid corrects neurological disease in a murine model of GM1 gangliosidosis,” by Christian Hinderer, M.D., Ph.D., and colleagues, including gene transfer pioneer Dr. Wilson, from the Gene therapy Program, Department of Medicine, University of Pennsylvania Perlman School of Medicine. The study in part was previously presented at the 22^nd annual Meeting of the American Society for Cell and Gene Therapy (ASCGT) in 2019.

This research evaluated the impact of single intracerebroventricular administration of the human β-gal containing AAV vector on β-galactosidase enzyme activity in the murine brain and peripheral tissues, lysosomal storage lesions, neurological function (including neurological exams and gait analysis) and survival in mice lacking the β-galactosidase gene. The mice received the single administration at age one month and were evaluated over 300 days. β-gal activity was increased significantly in the cerebral spinal fluid and serum of the vector-treated mice compared to vehicle control-treated mice. Significant improvements in gait assessments as measured by stride length and hind paw print length and significant preservation of neurological function as measured by neurological exam scores were observed throughout the study period in the human β-gal vector-treated mice. There were significant decreases in lysosomal storage lesions of vector-treated animals and by day 300 all animals that received the two highest doses were still alive, whereas none of the vehicle control-treated animals had survived.

“We’re excited about being able to soon advance PBGM01 into the clinic, and the potential promise it holds for patients with GM1, the majority of whom are infants and for whom there are no approved disease modifying treatments,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “Our plan is to administer PBGM01 through intra-cisterna magna delivery into the brain, which we believe may offer several benefits in terms of safety, efficiency and distribution compared to other approaches.”

Passage Bio expects to initiate dosing of PBGM01 in a Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021 and remains on track to report initial 30-day safety and biomarker data late in the first half of 2021.

This research was supported by a research, collaboration and license agreement with Passage Bio. HGT 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 on the HGT website.