ALZ-801 (valiltramiprosate)
Our lead product candidate, ALZ-801, is a patented, orally administered prodrug of tramiprosate that is designed to inhibit amyloid oligomer formation, a key driver of Alzheimer’s disease.
ALZ-801 was developed to improve gastrointestinal tolerability and the pharmacokinetic profile of tramiprosate by allowing ALZ-801 to be absorbed through the gut wall and be metabolized into active tramiprosate after absorption into the bloodstream. The data from our oral ALZ-801 Phase 1 clinical program showed improved gastrointestinal tolerability and more consistent plasma levels.
Compelling value proposition of ALZ-801 tablet
ALZ-801 product profile
- Robust efficacy in cognition & daily function*
- Disease stabilized for 18-month trial duration
- Preserved hippocampal volume
- Persistent clinical benefits over 2.5 years
- Well-tolerated oral tablet ideally suited for AD patients & their families
- No brain edema observed in Phase 2 study
- Low incidence of mild transient nausea
- No burdensome IV infusions or need for MRI monitoring for brain edema
- Amyloid antibody successes validate targeting toxic amyloid
- Safety data highlight need for APOE4 testing linked to risk of ARIA
- MRI monitoring of ARIA
- Approved antibody labels highlight need for APOE genotyping
*Based on tramiprosate Phase 3 data in Mild AD APOE4/4 patients, may be improved based on superior profile of ALZ-801 vs. tramiprosate
AD Preceded by Long Silent Pre-Symptomatic Phase
Jack (2018) Alzheimers Dement
Valiltramiprosate (ALZ-801) profile superior to tramiprosate
Addition of valine substantially improved PK & tolerability in AD patients
- High, sustained brain levels ~40%*
- Lower inter-patient variability ~25%
- Improved GI tolerability vs. tramiprosate
- 265 mg tablet, twice daily fully inhibits Aβ oligomer formation
- Commercial-ready tablet in Phase 3 trial
*Brain to plasma ratio; GI – gastrointestinal
Accelerating the development of ALZ-801
We have built our ALZ-801 development program upon an extensive preclinical and clinical data set. ALZ-801 has an improved pharmacokinetic profile, and through our focus on APOE4/4 homozygous patients who carry a higher amyloid burden, we believe that patients will be less likely to be misdiagnosed with Alzheimer’s disease.
ALZ-801 biological pathway
Conversion into tramiprosate & valine evaluated in ADME and Phase 1 studies
Degenhardt (2016) Psychosomatics
High accuracy of Alzheimer’s disease diagnosis in APOE4 subjects
- Correlation of APOE4 genotype with amyloid positivity on positron emission tomography (PET) in 370 subjects with clinical diagnosis of Mild to Moderate AD
- High diagnostic confidence that APOE4 patients have AD pathology addressable by anti-amyloid treatments
ALZ-801 effects observed in Phase 2 biomarker study
Final analysis at 24 months shows industry-leading efficacy in Early AD
- ALZ-801 treatment stabilized clinical progression in APOE4 AD carriers with high levels of amyloid & tau pathology
- ALZ-801 benefits in line with prior tramiprosate data
- Reduction in rate of hippocampal atrophy compared to ADNI consistent with AD disease modification modification
- Clinical benefits robustly correlated with brain volume preservation
- Biomarker data strongly point towards improved clearance of Aβ from brain to plasma
- Supports anti-oligomer action of ALZ-801 that maintains Aβ in soluble monomeric form
- Durable statistically significant plasma p-tau181 lowering supports downstream effects on AD pathology
- Phase 2 safety data continued to show favorable safety profile of ALZ-801 with no organ toxicity or ARIA-E events in APOE4 carrier population
Plasma p-tau181 reduction predicts clinical efficacy
