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.
| 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 |
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
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
- Injectable formulation for subcutaneous administration
- Sustained release mechanism over 7+ days
- Reduced injection frequency compared to traditional apomorphine delivery
- Potential for outpatient management
| 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 |
-
Primary Endpoints:
- Safety and tolerability
- Pharmacokinetic parameters
- Motor symptom improvement (OFF time reduction)
-
Secondary Endpoints:
- ON time with good mobility
- UPDRS scores (Part II and III)
- Quality of life measures (PDQ-39)
- Dyskinesia assessment
- Age 40-80 years
- Diagnosis of Parkinson's disease
- Motor fluctuations (ON/OFF episodes)
- Previous levodopa response
- Stable medication for ≥4 weeks
- Active psychiatric disease
- Severe dementia
- Previous apomorphine intolerance
- Active malignancy
- Significant medical conditions
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
These complications significantly impact quality of life and represent a major therapeutic challenge.
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)
SER-252 Advantage:
- 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
- Safety and tolerability: Adverse event monitoring, vital signs, laboratory values
- Pharmacokinetic parameters: Cmax, AUC, half-life, steady-state concentration
- Motor symptom improvement: OFF time reduction as measured by patient diaries
- 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
- 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
- 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
- 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
- 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
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 |
The polymer conjugation provides several pharmacokinetic benefits:
- Extended half-life: Reduced clearance through slowed renal elimination
- Stable plasma levels: Reduced peak-to-trough fluctuation
- Sustained exposure: Maintains therapeutic concentrations between doses
- Reduced injection burden: Fewer subcutaneous injections required
- 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
- 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
- Phase I/II clinical trial ongoing (NCT07422675)
- Enrollment progressing at multiple sites
- Active safety monitoring through Data Safety Monitoring Board
- 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
- Phase II/III trials pending Phase II results
- Regulatory interactions anticipated in 2026
- Commercial development partnership discussions
- 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
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
| 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.
- Biotechnology company focused on polymer-drug conjugates
- Platform technology for sustained drug delivery
- Pipeline focused on CNS disorders
- Additional polymer-conjugated therapeutics in development
- Apomorphine platform expansion
- CNS delivery technologies