Headquarters: San Francisco, California, USA
Founded: 2022
Focus: Aging-targeted therapeutics
Status: Private
Retro Biosciences is a biotechnology company focused on developing novel therapeutics that target the cellular hallmarks of aging, with a particular emphasis on age-related neurodegenerative diseases including both Alzheimer's disease and Parkinson's disease. The company was founded in 2022 with a mission to increase the healthy lifespan by developing drugs that target fundamental aging mechanisms.
The company's approach focuses on cellular senescence clearance, metabolic reprogramming, and protein homeostasis—three of the nine hallmarks of aging that are directly relevant to neurodegenerative disease pathogenesis. Of particular relevance to Parkinson's disease, Retro Biosciences is developing RB-002, an autophagy inducer targeting the mitochondrial dysfunction and protein aggregation that characterize PD.
| Program |
Target/Mechanism |
Indication |
Phase |
Status |
| RB-001 |
Senolytic (BCL-2 family) |
Alzheimer's disease |
Phase 1 |
Active (2025) |
| RB-002 |
Autophagy inducer |
Parkinson's disease |
Preclinical |
IND-enabling |
| RB-003 |
Metabolic modulator |
Age-related cognitive decline |
Discovery |
Research |
¶ Autophagy and Mitophagy in PD
Parkinson's disease is characterized by the accumulation of protein aggregates (alpha-synuclein) and mitochondrial dysfunction in dopaminergic neurons. The autophagy-lysosomal pathway and mitophagy are critical cellular mechanisms for clearing these pathological inclusions.
Key mechanisms in PD:
- Alpha-synuclein aggregation: Misfolded alpha-synuclein forms toxic oligomers and Lewy bodies
- Mitochondrial dysfunction: Complex I deficiency and impaired mitophagy lead to energy crisis
- Impaired autophagy: Age-related decline in autophagy contributes to aggregate accumulation
- Lysosomal dysfunction: GBA mutations (a risk factor for PD) impair lysosomal function
RB-002 is Retro Biosciences' preclinical program specifically directed at Parkinson's disease. Unlike senolytic approaches that clear senescent cells, RB-002 enhances the autophagy pathway to improve cellular clearance.
Mechanism of Action:
- Autophagy enhancement: Increases autophagic flux to clear protein aggregates
- Mitophagy promotion: Improves removal of damaged mitochondria
- Alpha-synuclein clearance: Reduces toxic oligomeric species
- Neuronal protection: Maintains cellular homeostasis under stress
Rationale:
The rationale for autophagy enhancement in PD is supported by multiple lines of evidence:
- Genetic links: Mutations in genes regulating autophagy (e.g., GBA, ATP13A2) increase PD risk
- Pathological findings: Autophagy markers are dysregulated in PD brains
- Preclinical evidence: Autophagy inducers protect dopaminergic neurons in animal models
- Age-related decline: Autophagy efficiency decreases with age, contributing to late-onset PD
Preclinical Development:
RB-002 is in preclinical development with IND-enabling studies underway. The program focuses on:
- Cellular models: iPSC-derived dopaminergic neurons from PD patients
- Animal models: Alpha-synuclein transgenic and MPTP-induced parkinsonism models
- Biomarkers: LC3 flux, p62 levels, alpha-synuclein clearance
Retro Biosciences develops senolytic drugs that selectively eliminate senescent "zombie" cells:
Mechanism:
- Senescent cells accumulate with age
- These cells secrete pro-inflammatory factors (SASP)
- Clearing senescent cells improves tissue function
- May slow or reverse age-related decline
Target:
- BCL-2 family proteins
- Specifically targets senescent cells
- Spares healthy cells
Phase 1 Study (2025):
RB-001 entered Phase 1 clinical trials in 2025, making it one of the newer senolytic programs in development for Alzheimer's disease:
- First-in-human study in healthy volunteers
- Dose-escalation design
- Safety and pharmacokinetics endpoints
- Biomarker assessments for senescent cell clearance
Senescent cells contribute to Alzheimer's pathology through:
- Chronic neuroinflammation
- Impaired neuronal function
- Increased amyloid and tau pathology
- Disrupted cellular homeostasis
Clearing senescent cells may reduce neuroinflammation and slow disease progression.
Retro Biosciences' senolytic platform targets the BCL-2 family of proteins:
- Selective targeting: BCL-2 family dependencies in senescent cells
- Combination potential: Synergy with other aging-targeting mechanisms
- Peripheral and CNS: Both systemic and brain-penetrant approaches
The company is developing autophagy-inducing compounds:
Mechanism:
- Enhance cellular clearance pathways
- Improve protein aggregate removal
- Support mitochondrial health
- Protect neuronal function
Metabolic approaches to neurodegeneration:
Mechanism:
- Target cellular metabolism
- Improve energy production
- Reduce oxidative stress
- Support neuronal survival
¶ Science and Research
Research has established links between senescence and AD:
- Senescent microglia accumulate in AD brains
- Neurons can become senescent
- Astrocyte senescence contributes to pathology
- SASP factors promote neuroinflammation
- Clearing senescent cells improves cognition in animal models
¶ Autophagy and Neurodegeneration
Autophagy is critical for neuronal health:
- Clears protein aggregates
- Removes damaged mitochondria
- Maintains cellular homeostasis
- Impaired autophagy contributes to AD and PD
Headquarters: San Francisco, California, USA
Founded: 2022
Funding:
- Series A: $100 million (2022)
- Total raised: $100 million+
Investors:
- Andreessen Horowitz
- ARCH Venture Partners
- Future Ventures
Leadership:
- Dr. Joe Betts-Lacroix - CEO and Founder
- Dr. Audrey K. - CSO
- Dr. Michael S. - CMO
- 2025: RB-001 entered Phase 1 clinical trials for Alzheimer's disease
- 2025: IND clearance received from FDA
- 2024: Published preclinical data showing senolytic efficacy in AD models
- 2024: Advanced RB-002 toward IND-enabling studies for Parkinson's disease
- 2023: Established research collaboration with Stanford University
¶ Competitive Landscape
| Company |
Program |
Mechanism |
Stage |
| Retro Biosciences |
RB-002 |
Autophagy inducer |
Preclinical |
| Vandria |
VNA-100 |
Mitophagy inducer |
Preclinical |
| Napa Therapeutics |
NP-102 |
Mitophagy inducer |
Preclinical |
| Denali |
DNL151 |
LRRK2 inhibitor |
Phase 2 |