AVROBIO Presents New Preclinical Data on Lentiviral Gene Therapy Program for Pompe Disease at ASGCT 2020

AVROBIO’s optimized lentiviral vectors demonstrate significant glycogen reduction in the muscle and central nervous system of Pompe disease mouse model

Investigational New Drug (IND)-enabling proof-of-concept study for AVR-RD-03 for Pompe disease currently underway

CAMBRIDGE, MA, USA I May 14, 2020 IAVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced new preclinical data for AVR-RD-03 for Pompe disease showcasing how its lentiviral gene therapy approach may potentially correct Pompe disease manifestations in the muscle and central nervous system (CNS). The data will be presented today at the American Society of Gene & Cell Therapy (ASGCT) 23rd Annual Meeting.

AVROBIO’s optimized lentiviral vectors for Pompe disease include a proprietary Glycosylation-Independent Lysosomal Targeting (GILT)-tag technology, which consists of a short peptide sequence linked to the therapeutic protein and is designed to enhance uptake in key tissues, and a potent transgene promoter to boost protein production. Data to be presented today demonstrate that AVROBIO-designed lentiviral vectors for Pompe disease incorporating GILT-tag technology significantly reduce toxic accumulation of glycogen in a mouse model of Pompe disease, including in cardiac and skeletal muscle, and the CNS. The toxic buildup of glycogen is caused by a mutation in the GAA gene and leads to a broad range of symptoms for people with Pompe disease, including progressive weakness, loss of motor function and trouble breathing. GAA encodes acid alpha-glucosidase, the enzyme that is functionally deficient in people living with Pompe disease.

“Our preclinical data strongly support the potential of our optimized lentiviral vector for Pompe disease with proprietary GILT-tag technology as a novel mechanism in the ‘head-to-toe’ treatment of Pompe disease, including symptoms that originate in the CNS,” said Chris Mason, M.D., Ph.D. AVROBIO’s chief scientific officer. “We feel a tremendous urgency to advance this therapy for people living with Pompe disease and look forward to completing the IND-enabling studies that could pave our path to the clinic.“

The study assessed 10 different lentiviral vectors with therapeutic transgenes in a mouse model of Pompe disease. Each vector was capable of producing expression of the GAA gene and included different versions of the GILT tag. Control vectors without a GILT tag were also tested. The presence of GILT tags substantially improved clearance of glycogen in the brain and spinal cord. The leading vector reduced glycogen in the cardiac muscle, the cerebrum and the spinal cord to levels that closely resembled those seen in wild-type mice. Glycogen content was also significantly reduced in heart, diaphragm and skeletal muscle tissue. Average vector copy number (VCN) in bone marrow was below five and there were no adverse effects seen on the hematopoietic compartment in treated mice. The mice were followed for four months after transplantation.

Based on these data, AVROBIO selected a candidate vector for progression into an Investigational New Drug-enabling proof-of-concept study, which is expected to conclude in 2020.

About Pompe disease

Pompe disease is a lysosomal disorder caused by a mutation in the GAA gene. The lack of the enzyme encoded by GAA results in a toxic buildup of glycogen throughout the body and central nervous system, causing a wide range of symptoms including progressive weakness and loss of motor function. Pompe disease affects about 1 in 58,000 Americans and is treated with enzyme replacement therapy, or ERT, which is typically given as a biweekly infusion for life. ERT slows but does not halt the overall progression of disease and does not cross the blood-brain barrier to address neurological pathologies. Even with ERT treatment, people with Pompe disease experience debilitating symptoms that reduce their quality of life.

About lentiviral gene therapy

Lentiviral vectors are differentiated from other delivery mechanisms because of their large cargo capacity and their ability to integrate the therapeutic gene directly into the patient’s chromosomes. This integration is designed to maintain the therapeutic gene’s presence as the patient’s cells divide, which potentially enables dosing of pediatric patients, whose cells divide rapidly as they grow. Because the therapeutic gene is integrated using the vector into patients’ stem cells ex vivo, patients are not excluded from receiving the investigational therapy due to pre-existing antibodies to the viral vector.


Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato™ gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.


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