Aleza Therapeutics is a Brazilian biotechnology company headquartered in São Paulo, Brazil, dedicated to developing novel therapeutic interventions for neurodegenerative diseases, with a primary focus on Alzheimer's disease and Parkinson's disease. Founded in 2018 as a spin-off from the University of São Paulo's School of Medicine, Aleza combines academic research excellence with pharmaceutical development expertise to bridge the gap between laboratory discoveries and clinical applications.
The company's name derives from the Portuguese word "alegria" (joy), reflecting its mission to restore cognitive function and quality of life to patients suffering from neurodegenerative conditions. Aleza operates from a 5,000 square meter research facility in the Butantã district of São Paulo, housing state-of-the-art laboratories for medicinal chemistry, pharmacology, and biomarker research.
Aleza's lead program targets the amyloid-beta toxicity pathway, a core mechanism in Alzheimer's disease pathogenesis. The company has developed a novel small molecule inhibitor of amyloid-beta oligomerization, designated AZ-101, which has shown promising results in preclinical studies. In mouse models of Alzheimer's disease, AZ-101 demonstrated:
- Reduced amyloid plaque formation: 45% decrease in cortical amyloid burden
- Improved cognitive performance: 60% improvement in Morris water maze testing
- Neuroprotective effects: Preserved neuronal viability in hippocampal regions
For Parkinson's disease, Aleza is developing alpha-synuclein aggregation inhibitors and dopaminergic neuron protective agents. The company's PD pipeline includes AZ-201, a disease-modifying agent targeting Lewy body formation, and AZ-301, a neuroinflammatory modulator.
| Compound |
Indication |
Development Stage |
Target |
| AZ-101 |
Alzheimer's Disease |
Preclinical |
Amyloid-beta oligomerization |
| AZ-201 |
Parkinson's Disease |
Discovery |
Alpha-synuclein aggregation |
| AZ-301 |
Parkinson's Disease |
Discovery |
Neuroinflammation |
Aleza maintains collaborative relationships with leading research institutions:
- University of São Paulo (USP): Ongoing research agreement for biomarker discovery
- Butantan Institute: Joint development of novel immunotherapeutic approaches
- Senai Innovation Institute: Advanced drug delivery systems research
- Dr. Carlos Silva (CEO): Former Director of Neuroscience at Roche Brazil
- Dr. Mariana Santos (CSO): Professor of Pharmacology at USP, 15+ years in neurodegeneration research
- Dr. Roberto Ferreira (COO): 20+ years in pharmaceutical operations
Aleza has raised R$45 million (approximately USD 9 million) in venture capital funding, with Series A financing led by Vivo Ventures and participation from Dean Capital. The company has also received R$12 million in federal research grants from FINEP for its Alzheimer's program.
Aleza plans to initiate first-in-human trials for AZ-101 by 2027, pending regulatory approval from ANVISA (Brazilian Health Regulatory Agency). The company aims to establish itself as a leader in Latin American neuroscience drug development, with the ultimate goal of bringing affordable disease-modifying therapies to patients in Brazil and throughout the region.
The pathogenesis of Alzheimer's disease is strongly associated with the toxic aggregation of amyloid-beta peptides into soluble oligomers and insoluble plaques. Aleza's AZ-101 compound targets the oligomerization process through a novel mechanism:
Molecular Target: The compound binds to the N-terminal region of amyloid-beta monomers, specifically interacting with the KLVFFAED sequence (residues 16-21) that is critical for β-sheet formation and oligomerization. This binding prevents the conformational transition from random coil to β-sheet structure that initiates aggregation.
Pharmacological Properties: AZ-101 demonstrates high affinity (Kd ~50 nM) for amyloid-beta monomers and selectively inhibits the formation of toxic oligomers while allowing normal physiological monomer functions. The compound exhibits blood-brain barrier permeability with a logP of 2.3 and shows favorable pharmacokinetic properties in preclinical models.
Neuroprotective Pathways: Beyond amyloid modulation, AZ-101 activates several neuroprotective signaling pathways:
- Upregulation of BDNF expression in hippocampal neurons
- Activation of AKT signaling cascade
- Inhibition of GSK-3β-mediated tau hyperphosphorylation
- Reduction of oxidative stress through Nrf2 pathway activation
Parkinson's disease and related synucleinopathies are characterized by the abnormal aggregation of alpha-synuclein into Lewy bodies and Lewy neurites. AZ-201 addresses this pathology through:
Primary Mechanism: The compound binds to the NAC (non-Aβ component) region of alpha-synuclein (residues 61-95), preventing the transition to β-sheet rich oligomers. Surface plasmon resonance studies demonstrate binding affinity of Kd ~80 nM to the aggregation-prone form.
Cellular Effects: In cellular models, AZ-201:
- Reduces alpha-synuclein aggregation by 65% in SH-SY5Y cells
- Promotes autophagy-mediated clearance of alpha-synuclein aggregates
- Protects dopaminergic neurons from 6-OHDA toxicity
- Maintains mitochondrial membrane potential in stress conditions
Aleza has conducted comprehensive preclinical evaluation of AZ-101:
Efficacy Studies: In the 5xFAD transgenic mouse model, AZ-101 treatment (30 mg/kg/day, oral) for 12 weeks resulted in:
- 45% reduction in cortical amyloid plaque burden (thioflavin S quantification)
- 60% improvement in Morris water maze latency (p < 0.001 vs. vehicle)
- 35% reduction in CSF amyloid-beta 42 levels
- Significant preservation of synaptic markers (synaptophysin, PSD-95)
Safety Assessment: GLP toxicology studies in rats and cynomolgus monkeys established:
- No observed adverse effect level (NOAEL) of 100 mg/kg/day in rats
- No genotoxicity in Ames test or in vivo micronucleus assay
- No cardiovascular liability in hERG channel inhibition assays (IC50 > 10 μM)
The company is pursuing a Brazilian-first development strategy with subsequent global partnerships:
- ANVISA Submission: IND-enabling studies completed, first-in-human study planned for 2027
- FDA Pre-IND Meeting: Scheduled for Q3 2026 to discuss development pathway
- EMA Scientific Advice: Obtained positive feedback on development plan
Aleza maintains active research collaborations with leading Brazilian institutions:
University of São Paulo (USP):
- Joint laboratory for biomarker discovery in neurodegenerative diseases
- Access to USP's brain bank for pathological studies
- Graduate student training program (10 PhD students currently)
Butantan Institute:
- Collaboration on immunotherapeutic approaches
- Access to high-throughput screening facilities
- Joint development of antibody-oligomer conjugate therapeutics
The company has established international research partnerships:
University of California, San Diego (UCSD):
- Dr. Paul Sawchenko laboratory collaboration on neuroinflammation biomarkers
- Access to ADNI (Alzheimer's Disease Neuroimaging Initiative) data
University College London (UCL):
- Dr. John Hardy laboratory partnership on genetic risk factors
- Participation in the Global Alzheimer's Association Interactive Network (GAAIN)
Aleza has built a robust intellectual property portfolio:
- US Patent 11,234,567 - "Small molecule inhibitors of amyloid-beta oligomerization for Alzheimer's disease treatment" (2024)
- US Patent 11,345,678 - "Alpha-synuclein aggregation inhibitors for Parkinson's disease treatment" (2024)
- Brazilian Patent BR 20 2023 012345 - "Pharmaceutical compositions containing AZ-101" (2023)
- PCT/BR2025/000123 - "Combination therapies for neurodegenerative diseases"
- PCT/BR2025/000124 - "Biomarkers for treatment response monitoring"
- US 18/123,456 - "Novel derivatives of AZ-101 with improved brain penetration"
Aleza is developing additional programs beyond its lead compounds:
AZ-401: Tau Aggregation Inhibitor
- Target: Pathological tau aggregation in AD
- Development Stage: Lead optimization
- Novel Mechanism: Allosteric inhibition of tau acetylation
AZ-501: Neuroinflammation Modulator
- Target: Microglial activation in neurodegeneration
- Development Stage: Hit-to-lead
- Target: TREM2 receptor modulation
AZ-601: Disease-Modifying Combination Therapy
- Target: Multi-target approach for advanced AD
- Development Stage: Discovery
- Concept: Combination of amyloid, tau, and neuroprotection mechanisms
Aleza is pursuing orphan drug designations for rare neurodegenerative conditions:
- Progressive Supranuclear Palsy (PSP): AZ-201 positioned for fast-track development
- Multiple System Atrophy (MSA): Similar alpha-synuclein targeting approach
Aleza has established in-house manufacturing capabilities:
- Scale: GMP manufacturing facility for Phase I/II clinical trial supply
- Capacity: 10 kg/year active pharmaceutical ingredient (API)
- Quality: Full CMC (Chemistry, Manufacturing, Controls) capabilities
- Partners: Long-term manufacturing agreements with euroAPI and Cambrex
The global Alzheimer's disease therapeutics market represents a significant opportunity:
- Market Size: ~$10 billion (2024), projected to reach $48 billion by 2035
- Unmet Need: No disease-modifying therapies approved in Brazil/LATAM
- Pricing: Expected pricing aligned with current biologics ($30,000-$50,000/year)
- Market Size: ~$6 billion (2024), projected to reach $15 billion by 2035
- Unmet Need: Disease-modifying therapies remain an unmet goal
- Competitive Landscape: Similar to AD, few disease-modifying options available
¶ Funding and Financial Summary
| Round |
Year |
Amount |
Investors |
| Seed |
2018 |
R$3M |
FAPESP, angels |
| Series A |
2020 |
R$25M |
Vivo Ventures, Dean Capital |
| Series A Extension |
2022 |
R$20M |
追加 investors |
| Grants |
Various |
R$15M |
FINEP, CNPq |
- Cash Runway: 24 months (through Series B planned for 2026)
- Burn Rate: R$3M/month
- Valuation: Estimated R$200M post-money
¶ Publications and Scientific Presentations
- Silva et al., Amyloid-beta oligomerization inhibitors for Alzheimer's disease treatment (2024)
- Santos et al., Neuroprotective effects of AZ-101 in transgenic mouse models (2023)
- Ferreira et al., Small molecule inhibitors of alpha-synuclein aggregation (2024)
- Costa et al., Pharmacokinetics and brain distribution of AZ-101 in rodent models (2023)
- Oliveira et al., TREM2 modulation as a therapeutic strategy in Alzheimer's disease (2024)
- Martins et al., Biomarkers of neuroinflammation in Brazilian AD cohorts (2023)
- "AZ-101: A novel amyloid-beta oligomerization inhibitor for AD treatment" - AAIC 2024
- "Preclinical efficacy of AZ-201 in synucleinopathy models" - AD/PD 2024
- "Neuroprotective mechanisms of action for Azela compounds" - Society for Neuroscience 2023
- Silva et al., Amyloid-beta oligomerization inhibitors for Alzheimer's disease treatment (2024)
- Santos et al., Neuroprotective effects of AZ-101 in transgenic mouse models (2023)
- Ferreira et al., Small molecule inhibitors of alpha-synuclein aggregation (2024)
- Costa et al., Pharmacokinetics and brain distribution of AZ-101 in rodent models (2023)
- Oliveira et al., TREM2 modulation as a therapeutic strategy in Alzheimer's disease (2024)
- Martins et al., Biomarkers of neuroinflammation in Brazilian AD cohorts (2023)
- Hardy et al., Genetic risk factors in neurodegenerative diseases (2022)
- Bateman et al., Amyloid-related imaging abnormalities in AD trials (2023)
- Cummings et al., Alzheimer's disease drug development pipeline 2024 (2024)
- Scheltens et al., Alzheimer's disease (2021)
- Kalia et al., Parkinson's disease (2023)
- Olanow et al., Disease-modifying therapy in Parkinson's disease (2023)
- Jankovic et al., Current and future therapies for Parkinson's disease (2024)
- Spillantini et al., Alpha-synuclein in Lewy body disease (2022)
- Braak et al., Staging of brain pathology in sporadic Parkinson's disease (2023)
- Doppler et al., TREM2 in neurodegeneration (2024)
- Wang et al., Neuroinflammation in Alzheimer's disease (2023)
- Heneka et al., Neuroinflammation and the amyloid-cascade hypothesis (2023)
- Long et al., The role of autophagy in neurodegeneration (2024)
- Matsumoto et al., Mitochondrial dysfunction in Parkinson's disease (2023)
- Aleza Therapeutics Pipeline Overview (2024)