Arvinas Therapeutics

<div class="infobox infobox-company">
<div class="infobox-header">Arvinas Therapeutics</div>
<div class="infobox-row"><strong>Headquarters:</strong> New Haven, Connecticut, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2013</div>
<div class="infobox-row"><strong>Ticker:</strong> NASDAQ: ARVN</div>
<div class="infobox-row"><strong>Focus:</strong> PROTAC Protein Degradation</div>
<div class="infobox-row"><strong>Status:</strong> Public (NASDAQ)</div>
</div>

Overview

<div class="infobox infobox-company">
<div class="infobox-header">Arvinas Therapeutics</div>
<div class="infobox-row"><strong>Headquarters:</strong> New Haven, Connecticut, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2013</div>
<div class="infobox-row"><strong>Ticker:</strong> NASDAQ: ARVN</div>
<div class="infobox-row"><strong>Focus:</strong> PROTAC Protein Degradation</div>
<div class="infobox-row"><strong>Status:</strong> Public (NASDAQ)</div>
</div>

Overview

Arvinas Therapeutics is a clinical-stage biotechnology company pioneering the development of PROTAC (Proteolysis-Targeting Chimera) protein degraders for the treatment of cancer and neurodegenerative diseases. Founded in 2013 as a spinout from Yale University, Arvinas created the proprietary PROTAC platform that harnesses the body's own ubiquitin-proteasome system to selectively eliminate disease-causing proteins["@arvinas_corp"].

The company has established the most advanced pipeline of brain-penetrant PROTACs in the industry, with multiple programs targeting proteins central to Parkinson's disease and Alzheimer's disease including LRRK2, tau, and alpha-synuclein. In 2025, Arvinas achieved a major milestone by demonstrating that its LRRK2 degrader ARV-102 can penetrate the blood-brain barrier and degrade its target in humans — the first PROTAC to achieve this feat["@arvinas2025_bbb"].

Corporate Profile

| Attribute | Details |
|-----------|---------|
| Headquarters | New Haven, Connecticut, USA |
| Founded | 2013 (Yale University spinout) |
| IPO | September 2018 (NASDAQ: ARVN) |
| Market Cap | ~$1.5 billion (2025) |
| Employees | ~300 |
| CEO | John Houston, PhD |

PROTAC Platform Technology

Mechanism of Action

PROTACs are heterobifunctional molecules consisting of three components: (1) a ligand that binds the target protein, (2) a ligand that recruits an E3 ubiquitin ligase, and (3) a chemical linker connecting the two. By bringing the target protein into proximity with an E3 ligase, PROTACs trigger polyubiquitination and subsequent proteasomal degradation of the target[@bekes2022].

Key advantages over traditional small molecule inhibitors:

• Catalytic mechanism: One PROTAC molecule can degrade multiple target molecules
• Target undruggable proteins: Can target proteins lacking traditional binding pockets
• Complete protein elimination: Removes all protein functions including scaffolding roles
• Potential for lower dosing: Sub-stoichiometric concentrations can achieve near-complete degradation

Brain-Penetrant PROTACs

Arvinas has developed proprietary brain-penetrant PROTAC technology that enables oral delivery of degraders to the central nervous system. This platform has been validated in non-human primates where Arvinas demonstrated:

• Oral bioavailability and CNS penetration
• Dose-dependent target degradation in brain tissue
• Sustained degradation with once-daily dosing
• Differentiated pharmacology from kinase inhibitors

Neurodegeneration Pipeline

Arvinas has established the most advanced neurodegeneration PROTAC pipeline in the industry:

| Program | Target | Indication | Stage | Status |
|---------|--------|------------|-------|--------|
| ARV-102 | LRRK2 | Parkinson's Disease / PSP | Phase 1 | Active |
| ARV-102 | LRRK2 | Parkinson's Disease | Phase 1b (planned 2026) | Planning |
| Tau PROTAC | Tau | Alzheimer's Disease | Discovery | Research |
| alpha-synuclein PROTAC | alpha-synuclein | Parkinson's Disease | Discovery | Research |
| mHTT PROTAC | mutant Huntingtin | Huntington's Disease | Discovery | Research |

ARV-102 (LRRK2 Degrader) — Lead Program

ARV-102 is the most clinically advanced PROTAC for neurodegenerative disease and represents a first-in-class degrader targeting LRRK2 (leucine-rich repeat kinase 2), the most common genetic cause of familial Parkinson's disease.

Target Rationale:

• LRRK2 mutations cause approximately 5-10% of familial PD and 1-3% of sporadic PD
• Elevated LRRK2 kinase activity is implicated in both familial and idiopathic PD
• Unlike kinase inhibitors, PROTAC degradation eliminates all LRRK2 functions including scaffolding roles

• In non-human primates, ARV-102 achieved nearly 90% LRRK2 degradation in deep brain regions
• Dose-dependent, sustained degradation in both brain and peripheral tissues
• Oral bioavailability enabling once-daily dosing[@arvinas2025_bbb]

• First-in-human dosing initiated February 2024
• Positive Phase 1 data presented at 2025 International Congress of Parkinson's Disease
• Demonstrated blood-brain barrier penetration (confirmed by CSF drug levels)
• Achieved central and peripheral LRRK2 degradation in healthy volunteers
• Well tolerated with no serious adverse events[@arvinas2025_phase1]

• 2024: Phase 1 initiated (completed single ascending dose)
• 2025: Phase 1 multiple-dose data expected, Phase 1b planning
• 2026 H1: Planned Phase 1b trial in progressive supranuclear palsy (PSP)
• Post-PSP: Potential expansion to Parkinson's disease

Tau PROTAC Program

Arvinas is developing PROTACs targeting tau protein for Alzheimer's disease and other tauopathies. Tau pathology correlates strongly with cognitive decline in Alzheimer's, and current approaches (antibodies, aggregation inhibitors) have shown limited efficacy.

Approach:

• Selectively degrade pathological tau species
• Addresses both intracellular and extracellular tau
• Potential to modify disease progression rather than just symptoms

alpha-Synuclein PROTAC Program

Targeting alpha-synuclein for Parkinson's disease and related synucleinopathies. Alpha-synuclein aggregation into Lewy bodies is the hallmark pathology of PD, and current antibody approaches have struggled to achieve sufficient target engagement.

Approach:

• Degrade both monomeric and oligomeric alpha-synuclein
• Address intracellular aggregation at the source
• Complement extracellular antibody approaches

Strategic Partnerships

Arvinas has established strategic partnerships to advance its neurodegeneration programs:

| Partner | Programs | Deal Structure |
|---------|----------|----------------|
| Pfizer | Multiple CNS PROTACs | Research collaboration, option to acquire |
| Eli Lilly | Tau, alpha-synuclein | Development and commercialization rights |
| Bayer | Undisclosed CNS | Research collaboration |

Pfizer Partnership

Arvinas entered a strategic partnership with Pfizer in 2022 to develop multiple CNS-targeted PROTACs. Pfizer received options to acquire programs following certain development milestones. The collaboration leverages Pfizer's neuroscience expertise and global commercialization capabilities.

Eli Lilly Partnership

Eli Lilly partnered with Arvinas for the tau and alpha-synuclein PROTAC programs. Lilly brings expertise in Alzheimer's disease drug development and a established neuroscience commercial infrastructure.

Financial Highlights

| Year | Revenue | Cash & Equivalents | Key Events |
|------|---------|-------------------|------------|
| 2024 | $95M | $350M | ARV-102 Phase 1 ongoing |
| 2023 | $75M | $400M | Lilly partnership initiated |
| 2022 | $60M | $450M | Pfizer partnership initiated |

Key Financial Events:

• 2018: IPO raised $120M
• 2022: Pfizer partnership worth up to $2B in milestones
• 2023: Eli Lilly partnership worth up to $1.5B in milestones

Scientific Advisory Board

Arvinas benefits from a distinguished scientific advisory board including pioneers in targeted protein degradation:

• Craig Crews, PhD — Founder and Chairman, inventor of PROTAC technology, Yale University
• Raymond Deshaies, PhD — Former Senior Vice President, Amgen, co-inventor of PROTACs
• Leading academic experts in ubiquitin biology, medicinal chemistry, and neuroscience

Competitive Landscape

Arvinas competes with other companies developing protein degradation approaches for neurodegeneration:

| Company | Approach | Stage |
|---------|----------|-------|
| Arvinas | Brain-penetrant PROTACs | Phase 1 (ARV-102) |
| Bristol Myers Squibb | Cereblon modulators | Discovery |
| Kymera Therapeutics | STAT3 degrader | Phase 1 (oncology) |
| Monte Rosa Therapeutics | Molecular glue degraders | Discovery |
| Biogen | ASO, antibodies | Various |

Cross-References

• [Targeted Protein Degradation (PROTACs) — Therapeutics](/therapeutics/targeted-protein-degradation-protacs)](/therapeutics)
• [LRRK2 Gene](/genes/lrrk2)](/genes)
• [LRRK2 Protein](/proteins/lrrk2-protein)](/proteins)
• [Parkinson's Disease](/diseases/parkinsons-disease)](/proteins/parkin)
• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Alpha-Synuclein](/proteins/alpha-synuclein)](/proteins)
• [Tau Protein](/proteins/tau)

See Also

• [Arvinas Corporate Website](https://www.arvinas.com)
• [Arvinas Neuroscience Pipeline](https://www.arvinas.com/research-and-development/neuroscience/)
• [PROTAC Technology Platform](/therapeutics/protac-molecular-glue-neurodegeneration)](/therapeutics)
• [LRRK2 Inhibitors vs Degraders](/therapeutics/lrrk2-inhibitor-therapy)

External Links

• [Arvinas Investor Relations](https://ir.arvinas.com)
• [ClinicalTrials.gov](https://clinicaltrials.gov/search?cond=parkinson&intr=ARV-102)](/proteins/parkin)
• [PubMed Search: PROTAC neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=PROTAC+neurodegeneration)

References