The NCT05693982 trial is a Phase 2 clinical study evaluating ASN90, an oral O-GlcNAcase (OGA) inhibitor developed by Asceneuron, in patients with early Alzheimer's disease[1]. This trial represents one of three active OGA inhibitor Phase 2 programs (alongside FNP-223 in PSP and LY-3372689 in AD/PSP).
| Parameter | Value |
|---|---|
| Trial ID | NCT05693982 |
| Phase | Phase 2 |
| Status | Ongoing (as of early 2026) |
| Drug | ASN90 |
| Company | Asceneuron (Lausanne, Switzerland) |
| Indication | Early Alzheimer's Disease (MCI due to AD, mild AD dementia) |
| Enrollment | ~150 patients |
| Duration | 52 weeks treatment + 26-week follow-up |
| Primary Endpoints | Safety, tolerability, biomarker changes |
| Secondary Endpoints | Cognitive measures (ADAS-Cog14, ADCS-MCI-ADL), CSF tau biomarkers |
ASN90 inhibits O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc modifications from proteins including tau[2][3]:
ASN90 operates on the yin-yang relationship between O-GlcNAcylation and phosphorylation:
| Modification | Effect on Tau | Disease State |
|---|---|---|
| O-GlcNAcylation | Protective (blocks phosphorylation) | Reduced in AD brain |
| Phorylation | Pathological (promotes aggregation) | Elevated in AD brain |
By inhibiting OGA, ASN90 shifts the balance toward protective O-GlcNAcylation.
The trial enrolls patients with:
| Trial | Drug | Company | Indication | Phase | Key Difference |
|---|---|---|---|---|---|
| NCT05693982 | ASN90 | Asceneuron | Early AD | Ongoing | |
| NCT05063539 | LY-3372689 | Eli Lilly | AD | Completed (no cognitive benefit) | |
| NCT05682807 | LY-3372689 | Eli Lilly | PSP | Pure tauopathy | |
| NCT05649734 | FNP-223 | Ferrer | PSP | Pure tauopathy, larger cohort |
ASN90 demonstrated in preclinical studies:
1000-fold selectivity over OGT (O-GlcNAc transferase)
The preceding Phase I trial (NCT05463754) established:
The OGA inhibitor field (including LY3372689 MAGNOLIA) has demonstrated:
This highlights the challenge of translating mechanism to clinical outcome in AD.
A key question is whether ASN90 can show benefit in AD where:
This context makes the parallel PSP trials (FNP-223 PROSPER, LY3372689 LOTUS) important - they test OGA inhibition in pure tauopathies without amyloid co-pathology.
OGA inhibitor mechanism. Science Translational Medicine. 2023. ↩︎
O-GlcNAcylation in tauopathy. Nature Reviews Neurology. 2023. ↩︎