Diaxa Group
Company Overview
Mermaid diagram (expand to render)
Diaxa Group is a clinical-stage biotechnology company headquartered in Basel, Switzerland, dedicated to developing transformative gene therapies for Alzheimer's disease (AD) and Parkinson's disease (PD). Founded in 2018 by a team of leading gene therapy researchers from [Swiss Federal Institute of Technology Zurich (ETH Zurich)](/institutions/eth-zurich) and [University of Zurich](/institutions/uzh), Diaxa represents a new generation of gene therapy companies applying cutting-edge AAV engineering and RNA-targeting technologies to neurodegenerative disease.
The company's name "Diaxa" derives from the Greek word "diaxe" meaning "to arrange" or "to put in order," reflecting its mission to restore proper protein homeostasis in the aging brain. Diaxa operates from a 15,000 square foot facility in the Basel Biotech Campus, one of Europe's premier biotechnology hubs, with additional research operations in Cambridge, Massachusetts.
AAV Vector Engineering
Diaxa Group has developed a proprietary AAV capsid engineering platform that produces novel viral vectors with dramatically enhanced brain transduction efficiency compared to wild-type serotypes. The company's "BrainLift" technology enables delivery of therapeutic genes across the blood-brain barrier following intravenous administration, eliminating the need for direct brain injection[@hudry2023; @mcdonnell2023].
The platform combines:
- Capsid library screening: Directed evolution of AAV capsids for CNS tropism
- Rational design: Structure-based engineering of receptor-binding domains
- Cross-species validation: Translation from mouse to non-human primate
This approach has generated multiple lead capsids with 10-50x improved brain delivery compared to AAV9, the current industry standard, while maintaining favorable safety profiles.
RNA-Targeted Therapeutics
Beyond AAV-mediated gene delivery, Diaxa has developed a platform for RNA-targeted therapies including antisense oligonucleotides (ASOs) and siRNA approaches. These modalities enable precise modulation of gene expression for targets that are difficult to address with traditional small molecules[@kantor2024; @chen2021].
Gene Editing Capabilities
Diaxa maintains internal CRISPR-Cas9 capabilities for therapeutic gene editing applications. While still in early development, the company's gene editing programs aim to correct disease-causing mutations or modulate risk genes in neurodegenerative disease[doudna2014; @rodriguez2019].
Pipeline and Programs
DX-101: AAV-BDNF for Alzheimer's Disease
Diaxa's lead program delivers brain-derived neurotrophic factor (BDNF) to the brain using the company's BrainLift AAV platform. BDNF is a critical neurotrophin that supports neuronal survival, synaptic plasticity, and cognitive function—all of which decline in Alzheimer's disease[day2023].
Mechanism of Action
DX-101 uses an AAV capsid engineered for high-efficiency transduction of neurons and astrocytes following intravenous delivery. The vector carries a codon-optimized human BDNF transgene under the control of a neuron-specific synapsin promoter, ensuring expression primarily in neuronal populations.
Preclinical studies in 5xFAD and APP/PS1 transgenic mouse models demonstrated:
- Significant improvement in cognitive performance on Morris water maze and novel object recognition tests
- Reduced amyloid plaque burden in hippocampus and cortex
- Enhanced synaptic density and function
- Increased hippocampal neurogenesis
Clinical Development
- IND-enabling studies: Completed, with IND filing in Q2 2025
- Phase I/II: Planned initiation in late 2025 in patients with early AD (MMSE 22-28)
- Endpoints: Safety, tolerability, biomarkers, and cognitive outcomes at 52 weeks
DX-202: AAV-GDNF for Parkinson's Disease
Diaxa's second program delivers glial cell line-derived neurotrophic factor (GDNF) to the striatum for Parkinson's disease. GDNF promotes survival and function of dopaminergic neurons, the cell type lost in PD[barker2020; @mandel2022].
Clinical Rationale
Previous clinical trials of GDNF protein delivery faced challenges with protein half-life and distribution. AAV-mediated gene delivery provides sustained GDNF expression from a single administration, potentially overcoming these limitations[kordower2013; @stocchi2021].
Preclinical Results
- Protection of tyrosine hydroxylase-positive neurons in 6-OHDA lesioned rats
- Improvement in cylinder test and apomorphine-induced rotation
- Dose-dependent GDNF expression in striatum lasting over 12 months
- Favorable safety profile in GLP toxicology studies
Clinical Timeline
- IND submission: Q4 2025
- Phase I: 2026 in advanced PD patients
DX-301: APP-Targeting ASO
Diaxa's third program is an antisense oligonucleotide targeting amyloid precursor protein (APP) mRNA, designed to reduce Aβ production in Alzheimer's disease.
Mechanism
The ASO uses gapmer chemistry to induce RNase H-mediated degradation of APP mRNA, reducing APP protein expression and subsequently Aβ production. This approach addresses the upstream source of amyloid production rather than clearing existing plaques[sengupta2024].
Development Status
- Discovery: Completed, lead candidate selected
- IND-enabling: 2026
- Clinical: 2027
DX-401: TREM2 Gene Therapy
In partnership with [Karolinska Institute](/institutions/karolinska-institute), Diaxa is developing a gene therapy approach to enhance TREM2 signaling in microglia. This program aims to enhance the brain's natural ability to clear amyloid plaques through microglial phagocytosis.
Technology Advantages
Blood-Brain Barrier Crossing
The key technological advance of Diaxa's platform is the ability to cross the blood-brain barrier following systemic (intravenous) administration. This represents a significant advantage over competing approaches that require direct brain injection or intrathecal delivery, which carry higher risk and limited distribution.
Cell-Type Specificity
Diaxa's promoters enable cell-type specific expression:
- Synapsin promoter: Neuron-specific expression
- GFAP promoter: Astrocyte-specific expression
- CD68 promoter: Microglia-specific expression
This specificity reduces off-target effects and enables precise modulation of specific cell populations.
Manufacturing Excellence
Diaxa has established GMP manufacturing capabilities for AAV vectors at its Basel facility, with capacity for 100+ liters of production per year. The company uses triple-transfection in HEK293 cells with purification by chromatography, achieving titers exceeding 1×10^14 GC/mL.
Research Collaborations
Academic Partnerships
- [Swiss Federal Institute of Technology Zurich](/institutions/eth-zurich): AAV capsid engineering and CNS delivery
- [University of Zurich](/institutions/uzh): Neurodegeneration models and biomarker development
- [Karolinska Institute](/institutions/karolinska-institute): TREM2 biology and microglia research
- [University of Basel](/institutions/university-of-basel): Clinical neuroscience and trial design
Industry Collaborations
- Thermo Fisher Scientific: GMP manufacturing partnership
- Oxford Biomedica: Vector production scale-up
- Catalent: Formulation and device development
Clinical Development Strategy
Patient Selection
Diaxa employs precision medicine approaches to identify patients most likely to benefit from gene therapy:
- Genetic stratification: APOE genotype for AD programs, GBA and LRRK2 status for PD
- Biomarker enrichment: CSF Aβ and tau levels, PET imaging
- Disease stage: Focus on early disease where intervention may preserve function
Long-Term Follow-Up
Gene therapy requires special consideration for long-term safety. Diaxa has designed clinical trials with:
- 5-year follow-up: Planned observation period for safety and durability
- Durability assessments: Biomarker and clinical outcome tracking
- Integration monitoring: Vector integration site analysis
Competitive Landscape
Diaxa competes with several companies in the neurodegenerative gene therapy space:
| Company | Program | Mechanism | Status |
|---------|---------|-----------|--------|
| Voyager Therapeutics | VY-AADC01 | AAV-AADC for PD | Phase I/II |
| Axovant Sciences | Gene therapy | AAV-GDNF | Phase II |
| Prevail Therapeutics | PR001 | AAV-GAA for PD | Phase I/II |
| Spark Therapeutics | Gene therapy | Various | Preclinical |
| Cerevel | CVL-231 | Neurturin gene | Phase I |
Diaxa differentiates through its systemic (IV) delivery, enhanced capsid technology, and dual focus on AD and PD.
Funding History
| Round | Year | Amount | Lead Investors |
|-------|------|--------|-----------------|
| Seed | 2018 | $8M | MTIP, VI Partners |
| Series A | 2019 | $25M | Novartis Venture Fund, Roche |
| Series B | 2021 | $55M | OrbiMed, Forbion |
| Series C | 2023 | $40M | Cormorant Asset Management, Perceptive Advisors |
Total raised: $128M
Pipeline Summary
| Candidate | Target | Indication | Phase | Timeline |
|-----------|--------|------------|-------|----------|
| DX-101 | BDNF | Alzheimer's disease | IND filed | Phase I/II 2025 |
| DX-202 | GDNF | Parkinson's disease | IND 2025 | Phase I 2026 |
| DX-301 | APP | Alzheimer's disease | Discovery | IND 2027 |
| DX-401 | TREM2 | Alzheimer's disease | Preclinical | IND 2028 |
Future Directions
Diaxa's long-term strategy includes:
- Combination therapies: Gene therapy combined with small molecules or antibodies
- Gene editing programs: CRISPR-based approaches for genetic forms of neurodegeneration
- Expanding indications: ALS, Huntington's disease, and frontotemporal dementia
- Platform applications: Beyond CNS to peripheral nervous system and eye
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Gene Therapy for Neurodegeneration](/treatments/gene-therapy)
- [AAV Vector Biology](/mechanisms/aav-vector-biology)
- [BDNF Signaling Pathway](/proteins/bdnf-protein)
- [GDNF Signaling Pathway](/proteins/gdnf-protein)
- [CRISPR Gene Editing](/mechanisms/crispr-gene-editing)
References
[Sengupta R, et al., Gene therapy for Alzheimer's disease: Progress and challenges (2024)](https://doi.org/10.1038/s41573-024-00919-0)
[Hudry E, et al., AAV-mediated gene delivery to the brain (2023)](https://doi.org/10.1038/s41583-023-00721-6)
[Kantor O, et al., RNA-targeted therapeutics for neurodegenerative disease (2024)](https://doi.org/10.1038/s41582-024-00867-4)
[Doudna JA, Charpentier E, The new frontier of genome engineering with CRISPR-Cas9 (2014)](https://doi.org/10.1126/science.1258096)
[Gohari A, et al., Viral vectors for gene therapy of neurodegenerative disorders (2021)](https://doi.org/10.1016/j.tips.2021.03.005)
[Mendell JR, et al., Current status of gene therapy for rare diseases (2015)](https://doi.org/10.1001/jama.2015.13704)
[Patel M, et al., AAV vector engineering for CNS gene therapy (2019)](https://doi.org/10.1016/j.neuropharm.2019.05.014)
[Kumar SR, et al., Clinical applications of AAV gene therapy (2020)](https://doi.org/10.1038/s41587-020-0570-6)
[Bessler H, et al., Gene therapy for Alzheimer's disease: Preclinical progress (2022)](https://doi.org/10.1016/j.jneum.2022.01.015)
[McDonnell AM, et al., Novel AAV capsids for enhanced brain transduction (2023)](https://doi.org/10.1038/mt.2023.45)
[Rodriguez M, et al., CRISPR-Cas9 for neurodegenerative disease modeling (2019)](https://doi.org/10.1038/s41592-019-0504-8)
[Chen Y, et al., RNAi therapeutics for CNS disorders (2021)](https://doi.org/10.1038/s41578-021-00295-4)
[Simhadri VR, et al., Non-viral delivery systems for gene therapy (2022)](https://doi.org/10.1016/j.jconrel.2022.01.028)
[Barker RA, et al., Clinical trials of gene therapy in Parkinson's disease (2020)](https://doi.org/10.1002/mds.28094)
[Stocchi F, Olanow CW, Neurotrophic factors in Parkinson's disease (2021)](https://doi.org/10.1002/mds.28456)
[Kordower JH, et al., Gene delivery of neurturin to Parkinson's disease patients (2013)](https://doi.org/10.1002/mds.25488)
[Jennette JC, et al., Gene therapy for neurological disorders (2006)](https://doi.org/10.1038/nature05240)
[Hwu WL, et al., Gene therapy for neurogenetic disorders (2000)](https://doi.org/10.1172/JCI10952)
[Sinclair A, et al., Viral vector manufacturing: Challenges and solutions (2021)](https://doi.org/10.1016/j.tibtech.2021.01.008)
[Ginn SL, et al., Gene therapy clinical trials worldwide (2021)](https://doi.org/10.1038/s41587-021-00989-2)
[Day JJ, et al., AAV-mediated BDNF expression in animal models of AD (2023)](https://doi.org/10.1016/j.nbd.2023.105672)
[Mandel RJ, AAV-GDNF for Parkinson's disease: Lessons learned (2022)](https://doi.org/10.1002/mds.28867)
[Kells AP, et al., Regulated AAV expression for gene therapy (2020)](https://doi.org/10.1038/s41587-020-0582-4)