Valiltramiprosate/ALZ-801

Our lead product candidate, valiltramiprosate, is a patented, orally administered prodrug of tramiprosate that is designed to inhibit amyloid oligomer formation, a key driver of Alzheimer’s disease.

Valiltramiprosate was developed to improve gastrointestinal tolerability and the pharmacokinetic profile of tramiprosate by allowing valiltramiprosate to be efficiently absorbed through the gut wall and be metabolized into active tramiprosate after absorption into the bloodstream. The data from our oral valiltramiprosate Phase 1 clinical program showed improved gastrointestinal tolerability and more consistent plasma levels.

Value proposition of valiltramiprosate tablet


Mattke (2023) JPAD

Valiltramiprosate product profile

  • Investigational oral disease-modifying therapy for MCI & Mild dementia stages of Alzheimer’s
  • Precision-medicine focus on APOE4/4 homozygotes
  • Small molecule, oral tablet used twice-daily
    • Inhibits formation of toxic amyloid oligomers
  • Ongoing Phase 2 & Phase 3 long-term extensions
  • Pivotal APOLLOE4 Phase 3 trial readout in 3Q 2024
  • Favorable safety profile with over 3,000 patient exposures*
    • No increased risk of ARIA in APOE4 carriers observed in trials to date
*Safety data based on bridged safety dataset from previous studies of tramiprosate and Phase 1 & Phase 2 studies in valiltramiprosate; ARIA – Amyloid Related Imaging Abnormalities, representing brain edema & microhemorrhage

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 valiltramiprosate

  • We have built valiltramiprosate development program upon an extensive preclinical and clinical data set
  • Valiltramiprosate has an improved pharmacokinetic profile
  • We focus on APOE4/4 homozygous patients who carry a higher amyloid burden, we believe that patients will be less likely to be misdiagnosed

Valiltramiprosate biological pathway

Conversion into tramiprosate & valine evaluated in ADME and Phase 1 studies

ALZ-801 Biological Pathway

confidence that APOE4 patients have AD pathology

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

Impact of valiltramiprosate treatment in APOE4 carriers

  • Published results of Phase 2 open-label, single arm, biomarker study in APOE4 carriers with Early AD and positive CSF biomarkers (Hey et al, Drugs 2024) showed
    • Statistically significant plasma p-tau181 lowering at 104-week primary endpoint
    • Early plasma p-tau181 reduction started at 13 weeks
    • Significant p-tau181 reduction at every visit over 2 years (31-41%)
    • Significant reduction in plasma Aβ42 at 2 years
    • These biomarker effects support target engagement of valiltramiprosate
  • Clinical memory scores showed early improvement and remained stable over 2 years
  • Memory stabilization correlated significantly with less hippocampal atrophy at 2 years
  • Phase 2 safety remains favorable in ongoing Phase 2 long term extension
    • No organ toxicity or ARIA-E events up to 3 years of treatment
    • Main treatment related AE was nausea