Arvinas, Inc. · NASDAQ:ARVN
Arvinas — Stifel Webinar (February 2024)
15 slides from Arvinas's conference presentation, Feb 14, 2024
Slide 1: ARV-102: Arvinas' Oral LRRK2 PROTAC Degrader
ARV-102: Arvinas’ Oral LRRK2 PROTAC® Degrader Enabling clearance of pathologic proteins that cause neurodegenerative disease John Houston, Ph.D., Chairperson, Chief Executive Officer, and President Angela Cacace, Ph.D., Senior Vice President, Neuroscience and Platform Biology February 14, 2024
Slide 2: Safe harbor and forward-looking statements
Safe harbor and forward-looking statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential advantages and therapeutic benefi
Slide 3: PROTAC protein degraders combine the benefits of small molecules and gene-based knockdown technologies
PROTAC® protein degraders combine the benefits of small molecules and gene-based knockdown technologies Arvinas’ proteolysis-targeting chimera E3 ligase 1 Complex Formation: Recognizing disease causing protein of interest (PROTAC) degraders can: Target Protein 2 Protein Tagging: • Eliminate (rather
Slide 4: Our broad pipeline includes the first pivotal trials for PROTAC degraders
Our broad pipeline includes the first pivotal trials for PROTAC® degraders Program Therapeutic Area / Indication Preclinical Phase 1/1b Phase 2 Phase 3 VERITAC-2: vepdegestrant monotherapy 2L+ pivotal trial Vepdegestrant plus palbociclib and potentially other CDK4/6 inhibitors in 2La Vepdegestrant V
Slide 5: Neuroscience: High potential in an area of tremendous unmet need
Neuroscience: High potential in an area of tremendous unmet need Arvinas Neuroscience Pipeline Each year, >6 million PROTAC protein degraders have the potential to patients in the U.S. are diagnosed change the treatment paradigm in neurodegenerative with Alzheimer’s, Parkinson’s, and diseases Huntin
Slide 6: PROTAC-induced LRRK2 degradation as a potential treatment for idiopathic Parkinson's Disease and PSP
PROTAC®-induced LRRK2 degradation as a potential treatment for idiopathic Parkinson’s Disease and Progressive Supranuclear Palsy Human genetics and biology create a strong rationale for differential biology of PROTAC LRRK2 degraders • LRRK2 is a large multidomain scaffolding kinase Mutations in and
Slide 7: PROTAC induces degradation of LRRK2 in human iPSC-derived microglia, in human PBMCs, and impacts lysosomal pathway
PROTAC® induces degradation of LRRK2 in human iPSC-derived microglia, in human PBMCs, and impacts lysosomal pathway PROTAC-concentration induced degradation In human PBMCs, PROTAC LRRK2 degradation aligns with effects on of LRRK2 in human iPSC-microglia target & pathway engagement Target Engagement
Slide 8: Lysosome number is reduced in PD models and increased by LRRK2 knock out and by PROTAC degraders
Lysosome number is reduced in PD models and increased by LRRK2 genomic knock out and by PROTAC® degraders Lysosome number is reduced in PD patients* and LRRK2 PROTAC degrader induces increase in lysosome models number per cell compared to LRRK2 Inhibitor(s) Lysosome number is reduced in PD models,
Slide 9: LRRK2 PROTAC enhances lysosome-based degradation
LRRK2 PROTAC® enhances lysosome-based degradation (to improve lysosomal protein clearance in neurodegeneration) DQ-Red BSA can be used to monitor LRRK2 PROTAC enhances lysosome degradation lysosome-mediated degradation compared to the inhibitor DQ-BSA degradation 10 LRRK2 PROTAC Degrader Spot count
Slide 10: PSP genetics implicate LRRK2 in progression of disease; PROTAC degraders reduce pathologic tau
PSP genetics implicate LRRK2 in progression of disease LRRK2 PROTAC® degraders induce reduction of pathologic tau LRRK2 SNP implicated in progression accelerated time to LRRK2 PROTAC induces reduction of AD induced death by 1 year in PSP† pathologic tau compared to inhibitor Reduction of pathologic
Slide 11: Oral PROTAC LRRK2 degrader reaches multiple deep brain regions in non-human primates and degrades LRRK2
Arvinas’ oral PROTAC® LRRK2 degrader reaches multiple “deep brain” regions in non-human primates and degrades LRRK2 >85% LRRK2 degradation in deep brain regions of cynomolgus monkeys after oral dosing 200 87% 87% 89% decrease v decrease decrease v 150 v Cortex LRRK2 Protein (% of Vehicle) Striatum S
Slide 12: PROTAC LRRK2 degrader shows better target engagement, enhanced potency and pathway engagement versus a LRRK2 inhibitor
PROTAC® LRRK2 degrader shows better target engagement, enhanced potency and pathway engagement versus a LRRK2 inhibitor Iterative (catalytic) PROTAC advantage results stronger LRRK2 and lysosomal pathway engagement vs. a LRRK2 inhibitora LRRK2 PROTAC vs. Kinase Lysosomal Pathway Engagement inhibitor
Slide 13: Our LRRK2 degrader induces biomarker changes that reinforce confidence in the PROTAC mechanism
Our LRRK2 degrader induces biomarker changes that reinforce confidence in the PROTAC® mechanism of action in the brain and periphery PROTAC-induced reductions observed in key PK/PD of LRRK2 reduction in cortex and CSF lysosomal marker in cynomolgus monkey following oral dosing in cynos BMP reduction
Slide 14: PROTAC protein degraders have the potential to change the treatment paradigm in neurodegenerative diseases
PROTAC® protein degraders have the potential to change the treatment paradigm in neurodegenerative diseases Preclinically, LRRK2 PROTAC protein Arvinas Neuroscience Pipeline degraders: • Increase lysosome number and degradative • Potential to cross the blood brain barrier and capacity degrade diseas
Slide 15: Thank you - Team Arvinas!
Thank you - Team Arvinas! 15