Affiris AG
Overview
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companies_affiris["Affiris AG"]
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companies_affiris_0["Company Overview"]
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companies_affiris_1["Alpha-Synuclein Immunotherapy Pipeline"]
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companies_affiris_2["PD01A Lead Program"]
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companies_affiris_3["PD03A Second Program"]
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companies_affiris_4["Technology Platform: SafePep"]
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companies_affiris_5["Competitive Landscape"]
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...Affiris AG
Overview
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Affiris AG is an Austrian biotechnology company headquartered in Vienna, Austria, focused on developing novel immunotherapies for neurodegenerative diseases, particularly Parkinson's disease and related synucleinopathies. The company's proprietary SafePep技术 platform enables the development of therapeutic vaccines that target disease-specific protein aggregates, with lead programs targeting alpha-synuclein and tau pathology["@affiris"].
Affiris takes a unique approach by targeting post-translationally modified forms of alpha-synuclein, particularly phosphorylation at Ser129 (pSer129), which is a pathological hallmark of Lewy bodies and glial cytoplasmic inclusions in Parkinson's disease and related disorders["@pser129"].
Company Overview
| Attribute | Details |
|-----------|---------|
| Headquarters | Vienna, Austria |
| Founded | 2006 |
| Technology Platform | SafePep (therapeutic vaccine) |
| Focus | Neurodegenerative disease immunotherapies |
| Stage | Clinical-stage |
Alpha-Synuclein Immunotherapy Pipeline
PD01A — Lead Program
PD01A is Affiris's lead clinical program, a therapeutic vaccine targeting phosphorylated alpha-synuclein (pSer129)[@pd01a].
| Attribute | Details |
|-----------|---------|
| Target | Phosphorylated alpha-synuclein at Ser129 (pSer129) |
| Mechanism | Active immunization to generate anti-pSer129 antibodies |
| Indication | Parkinson's disease |
| Phase | Phase 1 completed, Phase 2 planning |
| Delivery | Subcutaneous injection |
Mechanism of Action
PD01A works by stimulating the immune system to produce antibodies that specifically recognize and bind to alpha-synuclein that has been phosphorylated at Ser129. This post-translational modification is highly enriched in pathological inclusions in Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy.
Key features:
- Designed to generate antibodies against pSer129, not native alpha-synuclein
- Aims to neutralize and clear pathological pSer129 species before they form inclusions
- May prevent cell-to-cell transmission of alpha-synuclein pathology
- Potential for disease modification rather than just symptomatic relief
Clinical Data
Phase 1 Study (NCT01882191):
- Results: PD01A was safe and well-tolerated in patients with Parkinson's disease
- Immunogenicity: Generated anti-pSer129 antibodies in the majority of vaccinated subjects
- Antibody persistence: Antibody titers persisted for at least 12 months post-vaccination
- Safety: No serious adverse events related to the vaccine[@voller]
Rationale for Targeting pSer129
Phosphorylation at Ser129 is particularly relevant as a therapeutic target because:
- Over 90% of alpha-synuclein in Lewy bodies is phosphorylated at Ser129
- pSer129 is relatively rare in healthy brains, providing target specificity
- pSer129 species are more prone to aggregation and toxicity
- Antibodies against pSer129 can distinguish pathological from physiological alpha-synuclein
PD03A — Second Program
PD03A is Affiris's second alpha-synuclein vaccine program, also targeting phosphorylated alpha-synuclein but using a different antigenic design.
| Attribute | Details |
|-----------|---------|
| Target | Alpha-synuclein (phosphorylated forms) |
| Mechanism | Active immunization |
| Indication | Parkinson's disease, Multiple System Atrophy |
| Phase | Phase 1 planned |
Differences from PD01A
PD03A was developed as a backup candidate with potentially improved immunogenic properties. The program remains in early development stages.
Affiris's SafePep technology platform enables the design of therapeutic vaccines that specifically target disease-associated protein conformations while minimizing immune responses against normal proteins.
Platform advantages:
- Conformational specificity: Targets specific disease-related protein conformations
- Reduced off-target effects: Minimizes immune response against normal protein
- Synthetic peptide design: Allows precise control over antigenic epitopes
- Scalable manufacturing: Recombinant peptide-based approach
Competitive Landscape
| Company | Drug | Mechanism | Phase |
|---------|------|-----------|-------|
| Affiris | PD01A | Anti-pSer129 vaccine | Phase 1/2 |
| Prothena | Prasinezumab | Anti-α-syn mAb | Phase 2 |
| Vaxxinity | UB-312 | Anti-α-syn vaccine | Phase 2 |
| AC Immune | ACI-35 | Anti-pTau vaccine | Phase 2 |
| Roche | Ricobendazole | α-syn aggregation inhibitor | Phase 1 |
Scientific Rationale
Why Alpha-Synuclein?
Alpha-synuclein aggregation is central to Parkinson's disease pathogenesis. The protein undergoes nucleation-dependent polymerization from native monomers to toxic oligomers and fibrils that form Lewy bodies.
Therapeutic rationale:
- Reducing pathological α-synuclein may slow or halt disease progression
- Active vaccination offers potential for long-lasting protection with periodic boosters
- Targeting pSer129 provides specificity for pathological species
Why Active Immunization?
Active vaccination (therapeutic vaccines) offers several potential advantages over passive immunotherapy (monoclonal antibodies):
Durability: Single vaccination can generate months or years of antibody production
Cost: Potentially lower long-term treatment costs than repeated antibody infusions
Distribution: Endogenous antibodies may access tissues more effectively
Convenience: Subcutaneous administration rather than intravenous infusionCross-References
- [Alpha-Synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-aggregation-pathway)
- [Alpha-Synuclein Phosphorylation Mechanisms](/mechanisms/alpha-synuclein-phosphorylation-mechanisms)
- [Prion-Like Spreading](/mechanisms/prion-like-spreading)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Dementia with Lewy Bodies](/diseases/dementia-with-lewy-bodies)
- [Multiple System Atrophy](/diseases/multiple-system-atrophy)
- [Alpha-Synuclein Targeting Therapies](/therapeutics/alpha-synuclein-targeting-therapies)
- [Passive Immunotherapy](/therapeutics/antibody-therapy-neurodegeneration)
- [Prothena](/companies/prothena) — Anti-α-syn monoclonal antibody
- [Vaxxinity](/companies/vaxxinity) — UB-312 anti-α-syn vaccine
- [AC Immune](/companies/ac-immune) — Tau and amyloid vaccines
References
[Affiris Corporate Website](https://www.affiris.com)
[PD01A Phase 1 Study in Parkinson's Disease (2021)](https://doi.org/10.1016/j.jparkinson.2021.10.001)
[Phosphorylation at Ser129 is a pathological hallmark of α-synuclein inclusions (2004)](https://doi.org/10.1016/S0006-291X(04)02279-9)
[Voller et al., Affiris Phase 1 PD01A Study - J Parkinsons Dis (2021)](https://doi.org/10.3233/JPD-212890)
[Foukas et al., Active α-synuclein immunotherapy - Mov Disord (2022)](https://doi.org/10.1002/mds.29207)Pathway Diagram
The following diagram shows the key molecular relationships involving Affiris AG discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)