AZP2006 (Serazaxine) — PSP Platform Trial Therapy

AZP2006 (Serazaxine)

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">AZP2006 (Serazaxine) — PSP Platform Trial Therapy</th>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Design</td>
<td>Multicenter, randomized, double-blind, placebo-controlled, parallel-group</td>
</tr>
<tr>
<td class="label">Sites</td>
<td>3 sites in France</td>
</tr>
<tr>
<td class="label">Enrollment</td>
<td>41 screened, 36 randomized, 34 completed</td>
</tr>
<tr>
<td class="label">Population</td>
<td>Patients aged 40-80 years with probable or possible PSP</td>
</tr>
<tr>
<td class="label">Duration</td>
<td>12 weeks</td>
</tr>
<tr>
<td class="label">Dosing</td>
<td>60 mg QD, 80/50 mg QD, or placebo</td>
</tr>
<tr>
<td class="label">Primary Endpoints</td>
<td>Safety, tolerability, pharmacokinetics</td>
</tr>
<tr>
<td class="label">Secondary Endpoints</td>
<td>Pharmacodynamics (CSF/plasma biomarkers), PSP Rating Scale (PSPRS), Clinical Global Impression, Activities of Daily Living</td>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Participants</td>
<td>15 patients who completed Phase 2a</td>
</tr>
<tr>
<td class="label">Duration</td>
<td>6 months</td>
</tr>
<tr>
<td class="label">Results</td>
<td>No notable safety concerns; continued biomarker stabilization</td>
</tr>
<tr>

AZP2006 (Serazaxine)

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">AZP2006 (Serazaxine) — PSP Platform Trial Therapy</th>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Design</td>
<td>Multicenter, randomized, double-blind, placebo-controlled, parallel-group</td>
</tr>
<tr>
<td class="label">Sites</td>
<td>3 sites in France</td>
</tr>
<tr>
<td class="label">Enrollment</td>
<td>41 screened, 36 randomized, 34 completed</td>
</tr>
<tr>
<td class="label">Population</td>
<td>Patients aged 40-80 years with probable or possible PSP</td>
</tr>
<tr>
<td class="label">Duration</td>
<td>12 weeks</td>
</tr>
<tr>
<td class="label">Dosing</td>
<td>60 mg QD, 80/50 mg QD, or placebo</td>
</tr>
<tr>
<td class="label">Primary Endpoints</td>
<td>Safety, tolerability, pharmacokinetics</td>
</tr>
<tr>
<td class="label">Secondary Endpoints</td>
<td>Pharmacodynamics (CSF/plasma biomarkers), PSP Rating Scale (PSPRS), Clinical Global Impression, Activities of Daily Living</td>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Participants</td>
<td>15 patients who completed Phase 2a</td>
</tr>
<tr>
<td class="label">Duration</td>
<td>6 months</td>
</tr>
<tr>
<td class="label">Results</td>
<td>No notable safety concerns; continued biomarker stabilization</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>Finding</td>
</tr>
<tr>
<td class="label">Blood-brain barrier penetration</td>
<td>Confirmed — AZP2006 achieves CNS exposure in humans</td>
</tr>
<tr>
<td class="label">Target engagement</td>
<td>Demonstrated — progranulin levels stabilized in treated patients</td>
</tr>
<tr>
<td class="label">CSF biomarkers</td>
<td>Pharmacodynamic changes consistent with lysosomal pathway modulation</td>
</tr>
<tr>
<td class="label">Plasma pharmacokinetics</td>
<td>Dose-proportional exposure; long half-life supports QD dosing</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Target</td>
</tr>
<tr>
<td class="label">AZP2006</td>
<td>Progranulin / Lysosome</td>
</tr>
<tr>
<td class="label">[AADvac1](/therapeutics/aadvac1)</td>
<td>Tau</td>
</tr>
<tr>
<td class="label">[Lithium](/therapeutics/lithium-tauopathy)</td>
<td>GSK-3β</td>
</tr>
<tr>
<td class="label">[Tideglusib](/therapeutics/tideglusib-gsk3-inhibitor)</td>
<td>GSK-3β</td>
</tr>
<tr>
<td class="label">[Davunetide](/clinical-trials/davunetide-al108-psp)</td>
<td>Microtubule</td>
</tr>
<tr>
<td class="label">[Neflamapimod](/therapeutics/neflamapimod)</td>
<td>p38 MAPK</td>
</tr>
<tr>
<td class="label">[FNP-223](/therapeutics/fnp-223)</td>
<td>OGT</td>
</tr>
</table>

Overview

AZP2006 (development code; international nonproprietary name: serazaxine) is an oral pleiotropic neuroprotective drug developed by Aztherapi Ltd. It was selected for the PSP Platform Trial alongside [AADvac1](/therapeutics/aadvac1) based on Phase 2a results showing encouraging clinical and biomarker signals in patients with Progressive Supranuclear Palsy (PSP)[@corvol2025].

Unlike most PSP pipeline agents that target tau directly (antisense oligonucleotides, immunotherapies, O-GlcNAcylation modulators), AZP2006 works through a progranulin-dependent lysosomal pathway — a distinct mechanistic approach that aims to preserve synaptic function and slow neurodegeneration without directly engaging the tau pathology itself[@corvol2025].

Mechanism of Action

AZP2006's therapeutic effect is mediated through modulation of progranulin (PGRN) levels and consequent enhancement of lysosomal function[@corvol2025].

Progranulin Biology

[Progranulin](/entities/grn-gene) (gene: GRN, protein encoded) is a secreted glycoprotein with critical roles in neuronal survival, lysosomal function, and inflammation. Loss-of-function mutations in GRN cause a significant proportion of familial frontotemporal dementia, and progranulin deficiency is implicated in a broader range of neurodegenerative conditions including PSP and corticobasal syndrome[@corvol2025].

Key progranulin functions relevant to tauopathies:

• Lysosomal homeostasis: Progranulin regulates lysosomal biogenesis and function via transcription factor EB (TFEB) signaling. Impaired lysosomal function contributes to tau aggregation and propagation.
• Neuronal survival: Progranulin provides direct neurotrophic support to GABAergic and glutamatergic neurons.
• Neuroinflammation: Progranulin modulates microglial activation and the neuroinflammatory response that drives disease progression.

AZP2006's Mechanism

AZP2006 acts as an oral small molecule that upregulates progranulin expression and stabilizes circulating progranulin levels. This, in turn, enhances lysosomal clearance capacity, reduces accumulation of pathologic aggregates, and provides neuroprotection to vulnerable neuronal populations — particularly GABAergic neurons that are preferentially affected in PSP[@corvol2025].

The fact that AZP2006 does NOT directly target tau makes it a complementary mechanism to anti-tau therapies (AADvac1, E2814, BIIB080). Combining a progranulin/lysosome enhancer with an anti-tau immunotherapy represents a rational multi-target strategy for PSP[@corvol2025].

Clinical Trial Results

Phase 2a (NCT Primary Study)

Efficacy Results: Trends in efficacy favored slower disease progression in AZP2006 treatment groups vs. placebo, as measured by the PSP Rating Scale[@corvol2025].

Pharmacokinetics:

• Rapid absorption following oral dosing
• Long half-life: 60 mg cohort — 764.3 hours; 80/50 mg cohort — 684.7 hours
• Steady-state achieved by Day 45 (60 mg) and Day 28 (80/50 mg)[@corvol2025]

Open-Label Extension (OLE)

The 6-month OLE confirmed sustained safety and continued evidence of target engagement with stabilized progranulin levels[@corvol2025].

Safety and Tolerability

AZP2006 demonstrated acceptable tolerability and safety across all dosing cohorts[@corvol2025]:

• No treatment-related serious adverse events were reported during the 12-week Phase 2a
• No notable safety concerns emerged during the 6-month open-label extension
• The drug was administered orally, supporting patient convenience and compliance

Biomarker Evidence

The Phase 2a study incorporated extensive biomarker analyses:

PSP Platform Trial

AZP2006 was selected alongside [AADvac1](/therapeutics/aadvac1) (a tau-targeting active immunotherapy) for the PSP Platform Trial, an adaptive design study in PSP patients[@corvol2025]. This multi-arm platform design enables efficient evaluation of multiple therapeutic candidates simultaneously.

The complementary mechanisms — AZP2006 (progranulin/lysosome enhancement) + AADvac1 (anti-tau immunotherapy) — reflect a growing consensus that combination approaches will be needed to meaningfully slow PSP progression[@corvol2025].

See the [CBS/PSP Cure Roadmap](/mechanisms/cbs-psp-cure-roadmap) and [Tau-Targeted Therapeutics](/therapeutics/tau-targeted-therapeutics) pages for broader context on the PSP therapeutic landscape.

Comparison to Other PSP Therapies

AZP2006's MAPT-independent mechanism distinguishes it from the majority of PSP therapies, making it valuable as a complementary or rescue approach for patients who cannot tolerate or do not respond to anti-tau strategies.

Patient Relevance (CBS/PSP Context)

For patients with atypical parkinsonism (CBS/PSP spectrum):

Potential Advantages:

• Oral administration (vs. intrathecal or IV for many newer agents)
• Favorable safety profile — no serious treatment-related AEs
• Biomarker-confirmed target engagement and BBB penetration
• Novel mechanism not available through any approved therapy
• Complementary to anti-tau approaches — can be combined in future trials

• Phase 2a was small (n=36 randomized) — larger confirmatory trials needed
• Mechanism not fully characterized — progranulin modulation is established, but downstream pathways continue to be elucidated
• PSP Platform Trial enrollment is expected to expand the safety and efficacy dataset (results ~2027)
• Not yet FDA/EMA approved — currently available only through clinical trial participation

Key Publications

See Also

• [PSP Pathway](/mechanisms/psp-pathway)
• [CBS/PSP Cure Roadmap](/mechanisms/cbs-psp-cure-roadmap)
• [AADvac1 Tau Vaccine](/therapeutics/aadvac1)
• [Tau-Targeted Therapeutics](/therapeutics/tau-targeted-therapeutics)
• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Corticobasal Degeneration](/diseases/corticobasal-degeneration)
• [Progranulin (GRN Gene)](/entities/grn-gene)

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