Voyager Therapeutics, Inc. · NASDAQ:VYGR
Voyager Therapeutics — ASGCT 27th Annual Meeting 2024
15 slides from Voyager Therapeutics's conference presentation, May 8, 2024
Slide 1: Continued directed evolution of VCAP-101 and VCAP-102 identifies second generation capsids
Continued directed evolution of VCAP-101 and VCAP-102 identifies second generation capsids with increased brain tropism in non- human primates and mice (#119) Tyler Moyer, Ph.D Senior Scientist I, Novel Capsid Discovery ASGCT 27th Annual Meeting Breaking Barriers to the CNS via AAV Capsid Engineerin
Slide 2: Disclosure
Disclosure: Tyler Moyer is a full-time employee of Voyager Therapeutics. 2 |
Slide 3: VCAP-101 and VCAP-102 Demonstrate Increased CNS-Tropism Across Species
VCAP-101 and VCAP-102 Demonstrate Increased CNS-Tropism Across Species AAV9-based TRACERTM screen identifies VCAP-102 demonstrates increased CNS- VCAP-102 crosses the BBB through direct VCAP-101 and VCAP-102 as cross-species, tropism and liver detargeting and specific interaction with Tissue Non- BB
Slide 4: Gen2 Candidates were Selected for Increased CNS Tropism and Liver Detargeting
Gen2 Candidates were Selected for Increased CNS Tropism and Liver Detargeting Fitness Maturation Gen2 Candidates Selection Cterm Nterm Brain Transduction Liver Detargeting VCAP-101 or -102 3 1.6 1.4 Mouse Brain RNA Avg Fold 2.5 NHP Liver RNA Avg Fold 1.2 Change / VCAP-102 Change / AAV9 2 AAV9 1 Muta
Slide 5: Multiplexed Capsid Evaluation in NHP – Multi-Tag Approach
Multiplexed Capsid Evaluation in NHP – Multi-Tag Approach 3 mRNA Expression 1.38 50 3 1.5 %DAB+ Cells AAV9-Tg-Tag1 22 (Tag::TBP) 2 40 VG/DG 1.54 1.36 2 30 Motor Capsid A-Tg-Tag2 0.7 20 17 14 Cortex 0.8 1 9 1 0.3 0.5 10 4 Capsid B-Tg-Tag3 0.1 0.02 0.02 0.07 1 0 0 0 C dA C id B C id C C id D E ap V9 C
Slide 6: Multiplexed Capsid Evaluation in NHP – Multi-Tag Approach
Multiplexed Capsid Evaluation in NHP – Multi-Tag Approach 250 8.9 15 93 mRNA Expression 147 100 %DAB+ Cells 200 AAV9-Tg-Tag1 (Tag::TBP) 75 Liver VG/DG 150 10 32 30 Capsid A-Tg-Tag2 100 50 5 20 24 50 25 7 Capsid B-Tg-Tag3 15 13 15 9 2 0.2 0.4 0.7 0.4 0.2 0 0 0 C dA C id B C id C C id D E ap V9 Capsid
Slide 7: VCAP-Gen2 Transduces Cells Across Diverse Brain Regions
VCAP-Gen2 Transduces Cells Across Diverse Brain Regions Motor Purkinje DRG Caudate Putamen LGN Thalamus Heart Cortex Neurons Cervical %DAB+ Cells %DAB+ Cells Dose: Low Multi Multi Low Single High Low Multi Multi Low Single High Low Multi Multi Low Single High Low Multi Multi Low Single High Low Mult
Slide 8: VCAP-Gen2 Transduces Both Neurons and Astrocytes
VCAP-Gen2 Transduces Both Neurons and Astrocytes VCAP-Gen2 multi-tag 4E12 vg/kg Neurons VCAP-Gen2 single capsid at 3E13 vg/kg % NeuN+tag+ of total NeuN+ neurons 100 AAV9 VCAP-Gen2 VCAP-Gen2 Brain region multi-tag Multi tag single capsid %NeuN+ Tag+ Cells 80 Entorhinal Cortex 0 10 25 Hippocampus 0 4
Slide 9: VY9323 Demonstrates Upwards of 80% Knockdown of SOD1 mRNA in Spinal Cord Motor Neurons
VY9323 Demonstrates Upwards of 80% Knockdown of SOD1 mRNA in Spinal Cord Motor Neurons Cervical Spinal Cord Cervical Laser Captured Vehicle Motor Neurons anti-HA + anti-ChAT (0 vg/kg) SOD1 mRNA * 1.5 1.00 SOD1 mRNA Remaining (relative to vehicle) 1.0 50 µm 0.5 0.27 VY9323 (3E13 vg/kg) 0.0 23 cle 93
Slide 10: Iterative Capsid Evolution: Increased Brain Tropism and Liver Detargeting
Iterative Capsid Evolution : Increased Brain Tropism and Liver Detargeting Gen 1 Gen 2 AAV9 VCAP-102 VCAP-Gen2 IHC Liver Spatial Analysis IHC Cortex Spatial Analysis 10 |
Slide 11: VCAP-Gen2 Targets Neurons and Astrocytes in Mice
VCAP-Gen2 Targets Neurons and Astrocytes in Mice VCAP-Gen2 cellular expression of ssCAG-Transgene- Gen 1 Gen 2 HA in mouse cortex across a range of doses VCAP-102 VCAP-Gen2 70 60 % positive brain cells 50 40 30 20 Vector dose 10 0 Pre-analysis Post-analysis Pre-analysis Post-analysis Vector dose (vg
Slide 12: VCAP-Gen2 Expression in Mice Can Be Optimized Using Cell-Type Specific Promoters
VCAP-Gen2 Expression in Mice Can Be Optimized Using Cell-Type Specific Promoters CAG hSYN GFAP MAG Whole Brain Cortex Spinal Cord (Ventral Horn) Dosings were at 1E13 VG/kg of sc-ZsGreen-HA under the control of varying promoters; tail vein injection; 28 days in-life; 6-8 week old female Balb/c 12 |
Slide 13: Summary
Summary • VCAP-Gen2 is member of a family of second generation TRACERTM-derived capsids with increased CNS tropism relative to AAV9 in primates and mice. • This family of capsids utilizes the highly conserved receptor ALPL to cross the blood-brain barrier. • Up to 75% of cells were transduced across
Slide 14: Acknowledgements
Acknowledgements Capsid Discovery Team Histology Team Vector Production Team • Mathieu Nonnenmacher • Nilesh Pande • Kyle Grant • Brett Hoffman • Hamza Khalid • Jayashree Natasan • Kristin Graham • Anupriya Kulkarni • Ruohong Zhou • Matthew Child • Alexa Tsolias • Timothy Fiore • Roop Kaur • Amy Bru
Slide 15: Questions?
Questions? voyager
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