Compartmentalized Delivery of AAV Achieved in the Kidney
On-Target vs Systemic Drug Concentration
LRP Delivery System
Systemic Circulation
Group 21916 (1)AAV – Cocktail
(5 different serotypes)
4.9E+14 total vg
9.8E+13 vg per serotype
60-minute LRP
Sacrifice D15
9.8E+13 vg per serotype
60-minute LRP
Sacrifice D15
Closed-Loop Isolated Perfusion Dramatically Increases Target Organ Exposure vs. Systemic Route of Administration
DiNATEQ™ LRP system administration significantly increases AAV organ exposure vs intravenous
injection, thereby reducing dosage for treatment
injection, thereby reducing dosage for treatment
Group 21829 Key Findings
Area under the curve (AUC) ~200x greater for DiNATEQ™ LRP vs. IV at same total dose (i.e., sustained exposure).
Organ isolation and PK profile of DiNATEQ™ LRP delivery creates a new paradigm for capsid selection.
AAV gene therapy Cmax is ~100x higher when delivering the same dose via DiNATEQ™ LRP system versus intravenously.
Compartmentalized Delivery of AAV
Achieved in the Kidney
Achieved in the Kidney
Group 21831IV Injection
AAV-CAG-GFP
9.9E14 total vg, 1.1E+13 vg/kg Sacrifice D22
AAV-CAG-GFP
9.9E14 total vg, 1.1E+13 vg/kg Sacrifice D22
Group 21840
Group 21832Kidney DiNATEQ™ LRP
AAV -CAG-GFP
9.9E+14 total vg, 1.1E+13 vg/kg 1-hour procedure, Sacrifice D22
AAV -CAG-GFP
9.9E+14 total vg, 1.1E+13 vg/kg 1-hour procedure, Sacrifice D22
Relative kidney liver transduction increased by >600x through DiNATEQ™ LRP administration vs IV Adjusted for relative organ size, kidney: liver transduction increased by >7,000x
Group 21917
Group 21918 Direct Delivery System Safety Confirmed
in Large Animal Models
in Large Animal Models
Rectangle 2850 (4) Conducted a combined >80 acute and chronic LRP studies in the heart and kidney
- >90% procedural successful based on pre-defined study objectives
- Overall safety experience is excellent
- No evidence of compromise of either kidney or heart function
- Histologic findings minimal with no clinical impact
- Laboratory findings consistent with procedure and largely attributable to blood loss due to protocol (e.g., sampling schedule)
Systemic Safety
No Evidence of:
- Hepatotoxicity
- Hemolysis
- Inflammatory reactions
- Coagulation dysfunction
- Immune activation
image 11 (1)H&E of Pig Myocardium
Group 21851H&E of Pig Kidney Cortical Section
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