AVROBIO : ASGCT 2020 Preclinical Pompe Data Update

Hematopoietic Stem Cell Gene

Therapy Corrects Neuromuscular

Manifestations in Preclinical

Study of Pompe Mice

Session: Musculo-skeletal Diseases II

Niek van Til, PhD

AVROBIO, Cambridge, MA USA

May 14, 2020

Niek van Til is an employee of AVROBIO.

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Pompe is a lysosomal and glycogen storage disease

Rare, progressive, often fatal neuromuscular disorder

POMPE DISEASE

• Mutations in the acid alpha-glucosidase (GAA) gene resulting in deficient enzyme activity
• Leads to accumulation of glycogen in tissues and organs, predominantly in muscles
• Manifests as a spectrum of symptoms and rates of progression across patients of different ages
• • Infantile form (<1% GAA activity)
  • • Extreme muscle weakness, "floppy" appearance, enlarged heart, typically die before 1 year
  • Late / delayed onset form (2-40% GAA activity)
  • • Weakness of leg and hip muscles, become wheelchair-bound and ventilator-dependent, premature death
• The standard of care is enzyme replacement therapy

Normal muscle cell		Pompe disease (GAA mutation)
	Affected lysosomes		Affected muscle cells
Muscle fiber		Low acid α-glucosidase function		Lysosome & organelle dysfunction
	Glycogen storage disorder		Broad inflammation, muscle atrophy

Muscle cell

Lysosome

Over time

Cytoplasmic glycogen

Sources: van der Ploeg, Lancet, 2008	Patient images courtesy of the
patients/their families.	4