Valiltramiprosate/ALZ-801 potentially the first oral disease-modifying treatment for Alzheimer’s disease

Valiltramiprosate is well differentiated from plaque-clearing antibodies in development for Alzheimer’s disease, due to its novel mechanism of action, oral mode of administration, and potential efficacy in a genetically-targeted population. If our development program is successful and valiltramiprosate is approved, it could be the first oral disease-modifying drug for Alzheimer’s disease.

Valiltramiprosate precision medicine development approach

Fast-to-patient strategy seeking first approval in APOE4/4 homozygotes with Early AD following completion of APOLLOE4 Phase 3 trial

  • Leverage tramiprosate* safety & efficacy database, bridging to valiltramiprosate NDA
  • Efficient, well-powered confirmatory trial with NIA grant support
  • Precision medicine focus on patients with high risk of progression
  • Biomarker integration for confidence in therapeutic efficacy

Expansion to APOE3/4 heterozygotes & disease prevention

  • Phase 2 AD biomarker data to accelerate Phase 3 in APOE3/4 heterozygotes
  • Disease progression biomarkers as surrogates of efficacy to enable Phase 3 & supplemental NDA for AD prevention indication
*Active metabolite of valiltramiprosate, licensed by Alzheon from Bellus Health/Neurochem in 2013

Click to learn about APOLLOE4

Phase 3 study to evaluate efficacy of valiltramiprosate in APOE4/4 Early AD subjects

Initial focus on APOE4/4 patients based on valiltramiprosate mechanism of action

  • Greater diagnostic accuracy because >95% are amyloid & tau positive*
  • Strong biologic rationale: 3-fold higher levels of toxic Aβ oligomers in brain compared to non-carriers
  • Alzheimer’s clinical onset ~10 years earlier compared to non-carriers
  • Major unmet medical need
*Valiltramiprosate Phase 2 biomarker trial includes baseline CSF screening in APOE4/4 and APOE3/4 AD patients (data on file)

APOE4/4 homozygous

Valiltramiprosate oral tablet summary

Precision medicine Phase 3 program in Alzheimer’s

  • Differentiated product profile with first oral tablet advantage
    • Potentially disease-modifying efficacy & favorable long-term safety*
    • No increased risk of ARIA in APOE4 homozygotes or carriers over background rates, to-date
  • Clinically validated approach with high probability of success
    • Precision medicine focus of confirmatory APOLLOE4 Phase 3 trial
    • Biomarker-enabled program for accelerated development in additional indications
    • FDA Fast Track designation
  • Expansion to APOE4 carriers reaches over 13 million patients
    • APOE4 carriers with Early AD represent two-thirds of all AD patients
    • Planned prevention study at the pre-symptomatic stage
  • 24-month Phase 2 biomarker trial met primary endpoint of plasma p-tau181 reduction & supports disease modifying profile of oral valiltramiprosate**
  • Phase 3 topline readout in 3Q 2024
*Safety data based on bridged safety dataset from previous studies of tramiprosate and Phase 1 & Phase 2 studies in valiltramiprosate
**Phase 2 Topline Results: Hey et al, Drugs 2024
ARIA – Amyloid Related Imaging Abnormalities, brain edema & microhemorrhages

Valiltramiprosate Phase 3 trial in APOE4/4 patients with Early AD

APOLLOE4 pivotal trial fully enrolled with 325 subjects

ALZ-801 Alzheimer's medicine

Reflects current best internal estimates, subject to change; NDA – New Drug Application; sNDA – Supplemental New Drug Application; Phase 2 and Phase 3 studies continuing with Longterm Extension Studies (LTEs)

Valiltramiprosate development strategy