The Nex Step
in ERT
Technology:

NEXVIAZYME, an M6P-Enriched ERT

MECHANISM OF ACTION

NEXVIAZYME is an ERT for LOPD engineered with 15x more M6P than alglucosidase alfa.1,2,*

WHAT IS M6P?

Mannose-6-phosphate, or M6P, is a residue that binds to muscle cell receptors (called CI-MPRs), mediating the uptake of ERT into muscle cells.3-5

Engineered with 15x more M6P than alglucosidase alfa (Lumizyme)1,2
~15 mol M6P
per mol enzyme M6P NEXVIAZYME
~1 mol M6P
per mol enzyme Alglucosidase alfa

See how
NEXVIAZYME works

NEXVIAZYME enters the body by intravenous infusion1
1
Cell surface M6P on the surface of NEXVIAZYME binds onto muscle-cell
receptors
(CI-MPRs). This forms a NEXVIAZYME/CI-MPR complex1,3,6,7
2 Nexviazyme CI-MPR
Cell surface The formation of this complex helps internalize NEXVIAZYME into
the
cell and facilitates transport to the lysosome1,4
3
Inside the lysosome The NEXVIAZYME/CI-MPR complex dissociates and NEXVIAZYME
enters the lysosome, where it breaks down accumulated glycogen1,6,8
4 glycogen

NEXVIAZYME is engineered to have
~15 mol M6P per mol enzyme.
Alglucosidase alfa is engineered to have
~1 mol M6P per mol enzyme.1,2

NEXVIAZYME
Pharmacodynamics

Role in Glycogen Degradation

NEXVIAZYME demonstrated a reduction in urinary glucose tetrasaccharide (Glc4) levels during a phase 3 clinical trial.1

CHANGE IN URINARY GLC4 OVER 49 WEEKS

NEXVIAZYME™ (avalglucosidase alfa-ngpt) pharmacodynamic data Alglucosidase alfa (SD=32) NEXVIAZYME (SD=24) 0 -20 -60 -40

Mean percentage change in urinary Glc4 concentrations from baseline to week 49

The baseline mean urinary Glc4 concentration was 12.7 mmol/mol Cr and 8.7 mmol/mol Cr in NEXVIAZYME and alglucosidase alfa treatment groups, respectively.1

54%

reduction in urinary
Glc4 concentration
over 49 weeks in a
phase 3 clinical trial
in treatment-naive
patients with LOPD1

Urinary Glc4 concentrations
were normalized by urine
creatinine and reported as
mmol Glc4/mol creatinine.1

WHAT IS GLC4?

In patients with late-onset Pompe disease, excess glycogen is degraded to hexose tetrasaccharide (Hex4), which is then excreted in urine. The urinary Hex4 assay measures its major component, Glc4.1

OBSERVING GLC4 REDUCTIONS LONG-TERM

During the extended 145-week treatment period, urinary Glc4 was measured in patients who had been receiving NEXVIAZYME since baseline and in those who switched from alglucosidase alfa.1,9

URINARY Glc4 % CHANGE
FROM BASELINE 1,9

NEXVIAZYME Arm*

53% mean difference observed in urinary Glc4 from baseline to week 145 for those who remained on NEXVIAZYME1,9

Switch Arm

48% mean difference observed in urinary Glc4 from baseline to week 145 for those who switched to NEXVIAZYME1,9

*Nexviazyme Arm: Participants who received NEXVIAZYME in the PAP continued on NEXVIAZYME during ETP.
†Switch Arm: Participants who received alglucosidase alfa in the PAP and switched to NEXVIAZYME during ETP.

Cr=creatinine; PAP=primary analysis period; SD=standard deviation.