Prevail Therapeutics

Overview

Prevail Therapeutics is a US-based gene therapy company focused on developing treatments for neurodegenerative diseases. Founded in 2017 and headquartered in New York, NY, Prevail was acquired by Eli Lilly and Company in 2021 for approximately $880 million, becoming a wholly-owned subsidiary of Lilly["@eli2021"].

Overview

Prevail Therapeutics is a US-based gene therapy company focused on developing treatments for neurodegenerative diseases. Founded in 2017 and headquartered in New York, NY, Prevail was acquired by Eli Lilly and Company in 2021 for approximately $880 million, becoming a wholly-owned subsidiary of Lilly["@eli2021"].

Prevail's mission is to develop gene therapies that address the underlying genetic causes of neurodegenerative disorders, with initial focus on Parkinson's disease patients carrying GBA1 or LRRK2 mutations. Their AAV9-based platform enables delivery of therapeutic genes to the central nervous system["@prevail"].

Company Overview

| Attribute | Value |
|-----------|-------|
| Parent Company | Eli Lilly and Company |
| Founded | 2017 |
| Headquarters | New York, NY |
| Status | Subsidiary of Eli Lilly |
| CEO | Gillian H. Mayer (GM, Prevail) |

Acquisition by Eli Lilly

In December 2021, Eli Lilly announced the acquisition of Prevail Therapeutics for approximately $880 million ($22.50 per share)[@acquisition]. This acquisition:

• Provided Lilly with a gene therapy platform for neuroscience
• Gave access to Prevail's GBA1 and LRRK2 programs
• Expanded Lilly's Parkinson's disease pipeline
• Added AAV expertise and manufacturing capabilities

Funding History (Pre-Acquisition)

| Round | Year | Amount |
|-------|------|--------|
| Series A | 2017 | $30 million |
| Series B | 2019 | $75 million |

Pipeline Programs

PR001 (AAV-GBA1)

PR001 is Prevail's lead clinical program, an AAV9 gene therapy for Parkinson's disease patients with GBA1 mutations[@proview].

• Mechanism: Adeno-associated virus serotype 9 (AAV9) gene therapy delivering functional GBA1 gene
• Target: Glucocerebrosidase (GCase), encoded by GBA1 gene
• Phase: Phase 1/2 (PROVIEW trial)
• Indication: Parkinson's disease with GBA1 mutations
• Delivery: Intrathecal administration into cerebrospinal fluid
• Dose: Single administration

PROVIEW Trial

The PROVIEW trial is evaluating PR001 in Parkinson's disease patients with GBA1 mutations:

Patient Criteria:

• Confirmed Parkinson's disease diagnosis
• Confirmed GBA1 mutation (heterozygous)
• Hoehn & Yahr stage 2-3
• Age 40-75 years

• Primary: Safety and tolerability
• Secondary: Change in CSF GCase activity
• Exploratory: Change in CSF alpha-synuclein, clinical assessments (MDS-UPDRS)

PR004 (AAV-LRRK2)

PR004 is a preclinical gene therapy program targeting LRRK2-associated Parkinson's disease[@lrrk2021].

• Mechanism: AAV9 gene therapy delivering LRRK2-targeting construct
• Target: Leucine-rich repeat kinase 2 (LRRK2)
• Phase: Preclinical
• Indication: Parkinson's disease with LRRK2 mutations

Additional Pipeline

Prevail/Lilly's expanded pipeline includes:

• Gene therapy for other neurodegenerative indications
• Next-generation AAV capsids
• Combination approaches

Technology Platform

AAV9 Delivery

Prevail uses AAV9 capsids for CNS gene delivery because:

Manufacturing

As part of Lilly, Prevail leverages:

• GMP manufacturing facilities
• Scalable production processes
• Quality control systems
• Regulatory expertise

Science and Rationale

Why GBA1?

GBA1 mutations are among the most common genetic risk factors for Parkinson's disease:

• Heterozygous GBA1 mutations increase PD risk 5-6x
• GBA1 carriers have earlier onset and more severe symptoms
• GCase dysfunction leads to alpha-synuclein accumulation
• Restoring GCase function may slow disease progression

Why LRRK2?

LRRK2 mutations (particularly G2019S) cause autosomal dominant Parkinson's disease:

• Gain-of-function increases kinase activity
• LRRK2 inhibition/gene reduction is therapeutic in models
• Targeting the genetic cause may provide disease modification

Competitive Landscape

| Company | Drug | Mechanism | Phase |
|---------|------|-----------|-------|
| uniQure | AAV-GBA | Gene therapy | Phase 1 |
| Passage Bio | PBFT02 | AAVhu68-GBA | Phase 1 |
| Denali/Biogen | DNL151 | LRRK2 inhibitor | Phase 2b |
| Neurocrine | -- | Gene therapy | Discovery |

• [PD Pipeline Companies](/companies/pd-pipeline-companies)
• [Parkinson's Disease](/genes/ar)
• [Eli Lilly](/companies/eli-lilly)
• [GBA1](/proteins/gba1)
• [LRRK2](/proteins/lrrk2)
• [Alpha-Synuclein](/mechanisms/alpha-synuclein)
• [Gene Therapy](/therapeutics/gene-therapy)
• [Alzheimer's Disease](/diseases/alzheimers-disease) — Gene therapy pipeline](/genes/th)
• [Parkinson's Disease — GBA gene therapy](/genes/ar)
• [Gene Therapy for Neurodegeneration — AAV approaches](/genes/th)

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References