AMDX-2011P Retinal Amyloid Tracer in Alzheimer's Disease

Overview

AMDX-2011P is a novel retinal amyloid tracer being developed by Amydis Inc. for the non-invasive detection of amyloid deposits in the retina of [Alzheimer's disease](/diseases/alzheimers-disease) patients. This Phase 2 clinical trial evaluates the safety, tolerability, pharmacokinetics, and biological activity of AMDX-2011P as a potential diagnostic tool for Alzheimer's disease.

Trial Details

Overview

AMDX-2011P is a novel retinal amyloid tracer being developed by Amydis Inc. for the non-invasive detection of amyloid deposits in the retina of [Alzheimer's disease](/diseases/alzheimers-disease) patients. This Phase 2 clinical trial evaluates the safety, tolerability, pharmacokinetics, and biological activity of AMDX-2011P as a potential diagnostic tool for Alzheimer's disease.

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT06514001 |
| Status | RECRUITING (as of February 2026) |
| Phase | Phase 2 |
| Sponsor | Amydis Inc. |
| Intervention | AMDX-2011P 100 mg single bolus intravenous injection |
| Enrollment | 25 participants (estimated) |
| Study Design | Open-label, single-dose |

Study Objectives

Primary Objective

• Evaluate the safety and tolerability of AMDX-2011P in participants with Alzheimer's disease
• Assess the incidence and severity of adverse events over 8 days following administration

Secondary Objectives

• Characterize plasma pharmacokinetics (Cmax, AUC over 2 hours)
• Evaluate biological activity of AMDX-2011P as a retinal tracer
• Assess detection of retinal amyloid deposits at 8 days post-administration

Eligibility Criteria

Key Inclusion Criteria

Key Exclusion Criteria

Study Design

This is a Phase 2, open-label, single-dose study conducted at a single site:

• Site: Associated Retina Consultants, Phoenix, Arizona, USA
• Contact: Matthew Lehman (info@amydis.com, 859-905-0402)
• Duration: 8-day observation period per participant

Mechanism of Action

AMDX-2011P is designed as a retinal amyloid tracer that:

Rationale for Retinal Amyloid Imaging

The retina offers several advantages for Alzheimer's disease biomarker detection:

Significance for Alzheimer's Disease

This trial represents an important step in Alzheimer's disease diagnostics because:

Amyloid Biology Context

Amyloid-beta (Aβ) deposition is a hallmark pathological feature of Alzheimer's disease:

• [Amyloid Beta Peptide](/concepts/amyloid-beta-peptide) — The key protein fragment that aggregates into plaques
• [Amyloid Cascade Hypothesis](/mechanisms/amyloid-cascade-hypothesis) — The leading theoretical framework for AD pathogenesis

Related Pages

• [Retinal Imaging in Neurodegeneration](/diagnostics/retinal-imaging)
• [Optical Coherence Tomography in Neurodegeneration](/diagnostics/optical-coherence-tomography)
• [Amyloid PET Imaging](/diagnostics/pet-imaging) — Current standard for amyloid detection
• [APOE Genotyping for Neurodegenerative Disease Risk Assessment](/diagnostics/apoe-genotyping)
• [CSF Biomarkers in Neurodegeneration](/diagnostics/csf-biomarkers)
• [Plasma Biomarkers in Neurodegeneration](/diagnostics/plasma-biomarkers)
• [P-tau 217](/biomarkers/p-tau-217) — Other emerging AD biomarker
• [Clinical Trials Overview](/clinical-trials) — Index of all clinical trials
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Amydis Inc.](/organizations/amydis-inc)

Amyydis Inc. - Company Background

Company Overview

Amydis Inc. is a privately held biotechnology company founded in 2014 with a focus on developing non-invasive diagnostics for neurodegenerative diseases. The company's lead program targets retinal amyloid detection as a biomarker for Alzheimer's disease.

Technology Platform

Retinal Amyloid Detection:

• Proprietary fluorescent compounds that bind to amyloid deposits
• Designed for visualization via standard retinal imaging devices
• Non-invasive alternative to PET imaging
• Potentially lower cost than brain PET

• AMDX-2011P: Lead candidate for Alzheimer's disease (Phase 2)
• Early-stage programs for other neurodegenerative conditions
• Potential companion diagnostics for therapeutic development

Funding and Partnerships

• Raised Series A funding in 2016
• Received NIH grants for Alzheimer's diagnostic development
• Strategic partnership discussions ongoing
• Investigator-initiated trials at academic centers

Amyloid Biology and Retinal Deposition

Amyloid-Beta in Alzheimer's Disease Pathogenesis

The amyloid-beta peptide is central to Alzheimer's disease pathology:

APP Processing:

• Amyloid precursor protein (APP) is a transmembrane protein
• Beta-secretase (BACE1) cleaves APP to generate C99 fragment
• Gamma-secretase cleaves C99 to release amyloid-beta peptides
• Aβ40 and Aβ42 are most common species

• Aβ42 is more aggregation-prone than Aβ40
• Forms soluble oligomers, then fibrils, then plaques
• Oligomers are considered most toxic
• Plaques are pathological hallmark but may be protective

• Aβ accumulation is the initiating event
• Leads to tau pathology, neurodegeneration, cognitive decline
• Supported by genetic evidence (APP, PSEN1, PSEN2 mutations)
• Therapeutic targeting of Aβ has had mixed results

Retinal Amyloid Deposition

Evidence for Retinal Aβ:

• Retinal amyloid deposits documented in AD patients
• Correlate with brain amyloid burden on PET
• May precede cognitive symptoms
• Detectable via specialized imaging

• Direct access to CNS tissue (retina is brain-derived)
• Non-invasive imaging possible
• High resolution imaging available
• May allow earlier detection than brain imaging

• Quantification methods still developing
• Correlation with brain amyloid not perfect
• Standardization of imaging protocols needed
• Sensitivity compared to PET still being established

Study Design and Methodology

Phase 2 Study Design

NCT06514001 Details:

• Single-center, open-label study
• Single ascending dose design
• 25 participants with confirmed AD
• 8-day observation period

• Confirm AD diagnosis
• Verify positive amyloid PET
• Complete baseline assessments
• Obtain informed consent
• Safety laboratory evaluation
• APOE genotyping

• Complete physical examination
• Baseline retinal imaging (pre-dose)
• Vital signs and ECG
• Confirm eligibility

• Administer AMDX-2011P (100 mg IV)
• Monitor vital signs
• Collect PK samples
• Observe for acute reactions

• Daily vital signs
• Adverse event monitoring
• Retinal imaging at Day 8
• PK sampling schedule

• Safety assessment
• Final study visit

Imaging Protocol

Retinal Imaging Methods:

• Fundus photography
• Optical coherence tomography (OCT)
• Confocal scanning laser ophthalmoscopy (cSLO)
• Adaptive optics (research settings)

• Pre-dose baseline
• Day 8 post-dose (primary endpoint)
• Safety follow-up imaging

• Semi-quantitative amyloid detection
• Comparison to baseline
• Central reading by qualified ophthalmologist

Pharmacokinetic Sampling

PK Parameters to Evaluate:

• Cmax (maximum concentration)
• AUC (area under curve)
• Tmax (time to maximum)
• Half-life
• Clearance

• Blood samples at multiple timepoints
• Plasma separation within 30 minutes
• Storage at -80°C
• Bioanalysis by validated LC-MS/MS

Safety and Tolerability Assessment

Safety Endpoints

Primary Safety Variables:

• Incidence of adverse events (AEs)
• Serious adverse events (SAEs)
• Changes in vital signs
• Laboratory abnormalities
• ECG changes
• Ocular examination findings

• Severity (mild, moderate, severe)
• Relationship to study drug (unrelated, possibly related, probably related, definitely related)
• Expected vs. unexpected
• Serious vs. non-serious

Expected Adverse Events

Based on Compound Class:

• Injection site reactions (mild)
• Headache
• Nausea
• Transient visual changes
• Hypersensitivity reactions (rare)

• Continuous vital sign monitoring
• Pre- and post-dose ophthalmologic exams
• Daily safety laboratory evaluation
• Full physical examination at end of study

Safety Stopping Rules

Criteria for Study Interruption:

• More than 2 participants with drug-related severe AEs
• Any drug-related SAE
• Clinically significant laboratory abnormality
• Ocular safety signals

Biological Activity and Validation

Retinal Amyloid Detection

Detection Method:

• Fluorescent signal from bound compound
• Quantification of signal intensity
• Comparison to established thresholds
• Correlation with PET amyloid burden

• Detectable signal in amyloid-positive retinas
• Minimal signal in controls
• Dose-response relationship
• Correlation with PET SUVR

Amyloid PET Correlation

PET Imaging Standard:

• Standardized Uptake Value Ratio (SUVR)
• Centiloid scale for standardization
• Posterior cingulate/precuneus region
• Threshold: Centiloid >20 considered positive

• Compare retinal signal to PET SUVR
• Evaluate sensitivity and specificity
• Assess predictive value
• Determine optimal detection threshold

Biomarker Validation

Biomarker Qualification:

• Analytical validation of detection method
• Clinical validation in target population
• Correlation with clinical endpoints
• Establishment of reference ranges

Diagnostic Significance

Alzheimer's Disease Diagnostics Landscape

Current Diagnostic Challenges:

• Definitive diagnosis requires brain autopsy
• Clinical diagnosis has limited sensitivity/specificity
• Biomarkers improving but accessibility issues
• Need for early, accessible detection methods

• CSF Aβ42/tau ratio (invasive, specialized)
• Plasma Aβ and p-tau (emerging, accessible)
• Amyloid PET (expensive, radiation, limited access)
• FDG-PET for neurodegeneration
• Structural MRI for atrophy

Role of Retinal Imaging

Potential Advantages:

• Non-invasive (vs. LP for CSF)
• No radiation (vs. PET)
• Lower cost potential
• Accessible in ophthalmology settings
• Repeatable for monitoring

• Less established than PET
• Technical challenges in quantification
• Not yet validated for clinical use
• Requires specialized expertise

Clinical Utility

Potential Applications:

Implementation Considerations:

• Required imaging expertise
• Equipment availability
• Training for interpretation
• Standardized protocols
• Quality assurance

Future Development Plans

Phase 3 Registration Trial

Design Considerations:

• Larger sample size (hundreds to thousands)
• Multi-center international study
• Confirm sensitivity and specificity
• Compare to standard of care
• Regulatory submissions

• Diagnostic accuracy (sensitivity, specificity)
• Positive/negative predictive values
• Inter-reader reliability
• Safety in broader population

Companion Diagnostic Potential

Therapeutic Development Integration:

• Patient selection for anti-amyloid trials
• Treatment response monitoring
• Safety monitoring for amyloid-related effects
• Combination with therapeutic candidates

• CRO partnerships for large-scale studies
• Pharma collaboration for trial enrollment
• Diagnostic-therapeutic co-development
• Regulatory strategy alignment

Broader Applications

Other Neurodegenerative Diseases:

• Parkinson's disease (alpha-synuclein in retina)
• Dementia with Lewy bodies
• Vascular dementia
• Frontotemporal dementia
• Amyotrophic lateral sclerosis

• At-risk population screening
• Population-based testing
• Primary care integration
• Teleophthalmology potential

Regulatory Considerations

FDA Pathway

Diagnostic Device Classification:

• Class II medical device (if cleared)
• Requires 510(k) or De Novo submission
• Predicate device needed (or novel pathway)
• Clinical performance data required

• Breakthrough Device designation (potential)
• Parallel review with FDA and CMS
• Collaboration with professional societies
• Coverage determination discussions

Reimbursement Strategy

Medicare Coverage:

• LCD (Local Coverage Determination) process
• LCDD (Laboratory) vs. diagnostic imaging
• Evidence development pathway
• Clinical utility demonstration needed

• Medical necessity documentation
• CPT code development
• Reasonable and customary rates
• Prior authorization processes

Competitive Analysis

Other Retinal Diagnostics

| Company | Product | Target | Development Stage |
|---------|---------|--------|-------------------|
| Amydis | AMDX-2011P | Amyloid | Phase 2 |
| Cognoptix | Sapphire II | Amyloid | Research |
| Neurovision | Retinal imaging | Amyloid | Research |
| Neurodegeneration | Various | Tau, alpha-syn | Early |

Comparison to PET

Advantages over Amyloid PET:

• Lower cost (~$100 vs. ~$3000)
• No radiation exposure
• Faster (minutes vs. hours)
• More accessible
• Repeatable

• Less established
• Limited validation data
• May have lower sensitivity
• Technical expertise required

Molecular Imaging Mechanism

Fluorescence Detection Technology

AMDX-2011P utilizesfluorescence imaging to detect retinal amyloid deposits following intravenous administration:

Fluorescence Properties:

• Excitation wavelength: Optimized for retinal imaging devices
• Emission wavelength: Near-infrared for enhanced tissue penetration
• Quantum yield: High brightness for sensitive detection
• Photostability: Stable signal during imaging acquisition

Amyloid Binding Kinetics

The binding characteristics of AMDX-2011P determine detection sensitivity:

Association Kinetics:

• Rapid binding to amyloid aggregates
• High affinity (nanomolar Kd range)
• Slow off-rate for stable signal
• Preference for oligomeric and fibrillar species

• High selectivity for Aβ aggregates over monomers
• Minimal binding to other retinal proteins
• No significant lipofuscin interaction
• Preserved specificity in degenerating retina

Correlation with Brain Amyloid

The retinal amyloid burden correlates with cerebral pathology:

Cross-Sectional Correlation:

• Retinal Aβ correlates with PET amyloid burden
• Correlations strongest in mild-moderate disease stages
• Retinal imaging may reflect global brain amyloid load
• Regional specificity being investigated

• Retinal changes may precede brain changes in some cases
• Parallel disease progression in retina and brain
• Potential for earlier detection via retina

Clinical Validation Pathway

Regulatory Considerations

The development pathway addresses regulatory requirements:

Diagnostic Device Classification:

• Combination drug-device product
• Requires both drug and device clearance
• Companion diagnostic framework
• Biomarker validation requirements

• Demonstration of clinical impact
• Integration with standard of care
• Reimbursement pathway
• Clinical decision support utility

Comparison with Other Retinal Approaches

| Feature | AMDX-2011P | Structural OCT | Functional Testing |
|---------|-------------|---------------|--------------------|
| Target | Amyloid-specific | Structure | Function |
| Specificity | High (Aβ) | Moderate | Low |
| Disease specificity | High | Moderate | Low |
| Implementation | Medium | Low | Low |
| Regulatory status | Investigational | Approved | Approved |

Market Potential

Target Population:

• 6 million AD patients in US
• 55 million globally
• Early detection priority population
• Clinical trial enrichment

• Non-invasive detection alternative
• Reduced healthcare costs
• Population-wide screening potential
• Primary care implementation

Implementation Considerations

Healthcare System Integration:

• Ophthalmology practice settings
• Neurology referral pathways
• Primary care screening programs
• Clinical trial sites

• Reduced compared to PET imaging
• Population screening feasibility
• Early intervention enablement
• Care pathway optimization

Technical Specifications

Formulation Details

AMDX-2011P Formulation:

• Concentration: 100 mg single bolus
• Route: Intravenous injection
• Volume: 10 mL
• Vehicle: Sterile saline

Imaging System Requirements

Compatible Devices:

• Confocal scanning laser ophthalmoscopy (cSLO)
• Fundus camera with fluorescence capability
• Specialized retinal amyloid imaging systems
• Adaptive optics systems (research)

• Semi-quantitative scoring
• Quantitative fluorescence measurement
• Machine learning analysis
• Automated detection algorithms

Research Gaps and Future Directions

Unresolved Questions

Scientific Questions:

Clinical Questions:

Planned Studies

Future Clinical Development:

| Study | Phase | Timeline | Objectives |
|-------|-------|----------|------------|
| Phase 2b | Phase 2b | 2025-2026 | Doseoptimization |
| Phase 3 | Phase 3 | 2026-2028 | Pivotal efficacy |
| Confirmatory | Phase 3 | 2028-2029 | Validation |

Companion Diagnostic Development

Integration with Therapeutics:

• Anti-amyloid antibody combination
• Patient selection for trials
• Treatment response monitoring
• Treatment discontinuation decisions

Cross-Links

• [Retinal Biomarkers for Alzheimer's Disease](/biomarkers/retinal-biomarkers-alzheimers)
• [Amyloid PET Imaging](/technologies/amyloid-pet-imaging)
• [Retinal Imaging](/technologies/retinal-imaging-neurodegeneration)
• [Optical Coherence Tomography](/technologies/optical-coherence-tomography)
• [Amyloid-Beta](/proteins/amyloid-beta)
• [APOE Genotyping](/diagnostics/apoe-genotyping)
• [CSF Biomarkers](/biomarkers/csf-biomarkers-neurodegenerative-disease)
• [Blood Biomarkers](/biomarkers/plasma-biomarkers-alzheimers)
• [P-tau 217](/biomarkers/p-tau-217)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving AMDX-2011P Retinal Amyloid Tracer in Alzheimer's Disease discovered through SciDEX knowledge graph analysis: