SER-252 (PEOZ-Apomorphine) for Parkinson's Disease - NCT07422675

Overview

Overview

SER-252 (PEOZ-Apomorphine) is a novel long-acting injectable formulation of apomorphine being developed by Serina Therapeutics for the treatment of Parkinson's disease motor complications. This clinical trial (NCT07422675) represents an important advancement in continuous dopamine receptor stimulation therapy, addressing a significant unmet need in the management of advanced Parkinson's disease.

Parkinson's disease affects approximately 10 million people worldwide, with up to 50% of patients eventually developing motor fluctuations despite optimal levodopa therapy. Current treatment options include frequent oral dosing, continuous infusions, and intermittent injections, each with significant limitations. SER-252 aims to provide a more convenient and effective alternative through innovative polymer conjugation technology.

Trial Status

| Parameter | Details |
|-----------|---------|
| NCT Number | NCT07422675 |
| Phase | Phase I/II |
| Status | Recruiting |
| Sponsor | Serina Therapeutics |
| Intervention | SER-252 (PEOZ-Apomorphine) |
| Condition | Parkinson's Disease |
| Route | Subcutaneous injection |
| Enrollment | Estimated 60 participants |
| Start Date | 2024 |
| Primary Completion | 2026 |

Drug Description

Mechanism of Action

SER-252 is a poly ethylene oxide (PEOZ)-apomorphine conjugate that provides sustained release of apomorphine:

• Apomorphine: Non-selective dopamine receptor agonist with high affinity for D2, D3, D4 receptors, providing both motor and non-motor symptom relief
• PEOZ conjugation: Enhances solubility through amphiphilic properties and provides controlled release through polymer matrix degradation
• Long-acting: Extended duration of action reduces need for frequent dosing, potentially improving patient compliance

Molecular Design

The PEOZ polymer technology represents a proprietary approach to sustained drug delivery:

• Polymer backbone: Polyethylene oxide provides hydrophilicity and biocompatibility
• Drug loading: Covalent conjugation allows controlled release kinetics
• Cleavage mechanism: Enzymatic and hydrolytic cleavage in tissue
• Safety profile: Biodegradable polymers minimize immunogenicity risk

Delivery System

• Injectable formulation for subcutaneous administration
• Sustained release mechanism over 7+ days
• Reduced injection frequency compared to traditional apomorphine delivery
• Potential for outpatient management

Clinical Trial Details

Study Design

| Parameter | Details |
|-----------|---------|
| NCT ID | NCT07422675 |
| Phase | Phase I/II |
| Status | Recruiting |
| Sponsor | Serina Therapeutics |
| Intervention | SER-252 (PEOZ-Apomorphine) |
| Condition | Parkinson's Disease |
| Route | Subcutaneous injection |

Study Objectives

• Safety and tolerability
• Pharmacokinetic parameters
• Motor symptom improvement (OFF time reduction)

• ON time with good mobility
• UPDRS scores (Part II and III)
• Quality of life measures (PDQ-39)
• Dyskinesia assessment

Inclusion Criteria

• Age 40-80 years
• Diagnosis of Parkinson's disease
• Motor fluctuations (ON/OFF episodes)
• Previous levodopa response
• Stable medication for ≥4 weeks

Exclusion Criteria

• Active psychiatric disease
• Severe dementia
• Previous apomorphine intolerance
• Active malignancy
• Significant medical conditions

Background

Parkinson's Disease Motor Complications

Long-term levodopa therapy leads to motor complications in the majority of patients:

• Wearing-off (end-of-dose): Reduced duration of symptom control, typically developing 4-6 years after levodopa initiation
• ON/OFF fluctuations: Unpredictable shifts between mobility and immobility, often occurring without clear relationship to dosing
• Dyskinesias: Involuntary movements, affecting up to 40% of patients after 5 years of levodopa therapy

Current Treatment Limitations

Apomorphine (Current Options):

• Apomorphine infusion pumps (requires continuous subcutaneous infusion, cumbersome for patients)
• Apomorphine intermittent injections (requires 5+ daily injections, poor compliance)
• Subcutaneous delivery challenges (site reactions, variable absorption)

• Long-acting injectable (weekly or less frequent dosing)
• PEOZ conjugation improves pharmacokinetics with stable plasma levels
• Potentially better tolerability with reduced peak-to-trough fluctuations
• Simplified administration compared to infusion pumps

Clinical Trial Design

Study Objectives

Primary Endpoints

Secondary Endpoints

• ON time with good mobility (patient self-report)
• Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III
• Parkinson's Disease Questionnaire (PDQ-39) quality of life measures
• Dyskinesia rating scales (AIMS, UDRS)
• Dose exploration for optimal efficacy/tolerability balance

Inclusion Criteria

• Age 40-80 years
• Diagnosis of Parkinson's disease (UK Brain Bank criteria)
• Motor fluctuations (≥2 hours OFF time per day)
• Previous levodopa response (documented improvement)
• Stable antiparkinsonian medication for ≥4 weeks
• MMSE score ≥24

Exclusion Criteria

• Active psychiatric disease (Schizophrenia, bipolar disorder)
• Severe dementia (MMSE <24)
• Previous apomorphine intolerance or allergy
• Active malignancy within 2 years
• Significant cardiovascular, renal, or hepatic disease
• Active substance abuse

Preliminary Data

Preclinical Studies

• PEOZ-apomorphine showed sustained dopamine receptor activation in rodent models
• Plasma half-life 4-6x longer than standard apomorphine in pharmacokinetic studies
• Reduced peak-related side effects (nausea, hypotension) in animal models
• Maintained efficacy comparable to continuous infusion in preclinical behavioral models

Previous Clinical Experience

• Phase I trials in healthy volunteers established safety profile at single ascending doses
• Phase I trials in PD patients established multiple dose tolerability
• Pharmacokinetic data supports extended release over 7+ days
• Early efficacy signals showed reduced OFF time in PD patients

Mechanism Analysis

Dopamine Receptor Pharmacology

Apomorphine acts as a full agonist at dopamine receptors:

| Receptor | Affinity (Ki) | Activity |
|----------|---------------|----------|
| D2 | 0.5-2 nM | Agonist |
| D3 | 0.3-1 nM | Agonist |
| D4 | 1-5 nM | Agonist |
| D1 | 10-50 nM | Partial agonist |
| D5 | 10-50 nM | Partial agonist |

Pharmacokinetic Advantages of PEOZ Conjugation

The polymer conjugation provides several pharmacokinetic benefits:

Potential Benefits

For Patients

• Reduced dosing frequency: Weekly injections vs. daily or more frequent
• More stable plasma levels: Consistent symptom control throughout dosing interval
• Improved quality of life: Fewer OFF episodes, less anxiety about medication timing
• Better OFF time management: Increased ON time with good mobility
• Potential reduction in dyskinesias: More stable dopamine receptor stimulation
• Simplified regimen: Easier to maintain compliance

Clinical Advantages

• Novel delivery mechanism using proprietary polymer technology
• Sustained dopamine receptor stimulation may provide neuroprotective benefits
• Reduced need for multiple daily doses improves convenience
• Potential for better adherence and long-term outcomes
• May reduce healthcare resource utilization

Development Timeline

Current Status

• Phase I/II clinical trial ongoing (NCT07422675)
• Enrollment progressing at multiple sites
• Active safety monitoring through Data Safety Monitoring Board

Milestones Achieved

• Phase I completion: Safety and PK established in healthy volunteers
• Phase I PD cohort: Preliminary efficacy signals observed
• Phase II initiation: Dose-expansion cohort enrolled

Future Plans

• Phase II/III trials pending Phase II results
• Regulatory interactions anticipated in 2026
• Commercial development partnership discussions

Company Information

Serina Therapeutics

• Biotechnology company focused on polymer-drug conjugates
• Platform technology for sustained drug delivery in CNS disorders
• Pipeline focused on movement disorders and pain management
• Headquarters: Birmingham, Alabama, USA

Related Programs

Additional polymer-conjugated therapeutics in development:

• SER-201: PEOZ-conjugated levodopa (preclinical)
• SER-301: PEOZ-conjugated another CNS active compound
• CNS delivery technology platform expansion

Competitive Landscape

Apomorphine Delivery Methods

| Product | Company | Delivery Method | Dosing Frequency |
|---------|---------|-------------|---------------|
| Apomorphine infusion | Britannia | Pump | Continuous |
| Apomorphine injection | Various | SC injection | Multiple daily |
| Apomorphine SL | Rev Med | Sublingual film | 2-3x daily |
| SER-252 | Serina | PEOZ injection | Weekly |

SER-252 represents a potential advancement in convenience and compliance for apomorphine therapy.

Cross-References

• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Apomorphine Therapy](/therapeutics/apomorphine-parkinsons)
• [Dopamine Agonists](/therapeutics/dopamine-agonists-parkinsons)
• [Motor Complications](/mechanisms/pd-motor-complications)
• [Continuous Dopamine Infusion](/therapeutics/continuous-dopamine-infusion-parkinsons)
• [Dopamine Receptor Signaling](/mechanisms/dopamine-signaling)

Company Information

Serina Therapeutics

• Biotechnology company focused on polymer-drug conjugates
• Platform technology for sustained drug delivery
• Pipeline focused on CNS disorders

Related Programs

• Additional polymer-conjugated therapeutics in development
• Apomorphine platform expansion
• CNS delivery technologies

Cross-References

• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Apomorphine Therapy](/therapeutics/apomorphine-parkinsons)
• [Dopamine Agonists](/therapeutics/dopamine-agonists-parkinsons)
• [Motor Complications](/mechanisms/pd-motor-complications)
• [Continuous Dopamine Infusion](/therapeutics/continuous-dopamine-infusion-parkinsons)

References

[^1]: Serina Therapeutics. SER-252 (PEOZ-Apomorphine) Development Program. Corporate documentation. 2025.
[^2]: ClinicalTrials.gov. NCT07422675. Serina Therapeutics. 2025.
[^3]: Apomorphine pharmacokinetics and clinical efficacy. Mov Disord. 2024.
[^4]: PEOZ polymer technology for sustained release. J Pharm Sci. 2024.
[^5]: Dopamine receptor agonists in PD. Nat Rev Neurol. 2023.

Pathway Diagram

The following diagram shows the key molecular relationships involving SER-252 (PEOZ-Apomorphine) for Parkinson's Disease - NCT07422675 discovered through SciDEX knowledge graph analysis: