ALZ-801
An Improved Prodrug Formulation
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 in a prodrug inactive form and 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.
Improvements Enhance Prospects for ALZ-801 Efficacy & Safety
Accelerating the Development of ALZ-801
We have built our ALZ-801 development program upon the extensive preclinical and clinical data set for tramiprosate. ALZ-801 has an improved pharmacokinetic profile, and through our focus on APOE4/4 homozygous patients who carry a higher amyloid burden, 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
In October 2017, ALZ-801 was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of Alzheimer’s disease. We plan to initiate a Phase 3 trial for ALZ-801 in APOE4/4 homozygous patients with mild Alzheimer’s in 2019. This trial will be an 18-month, double-blind, placebo-controlled Phase 3 trial in APOE4/4 homozygous patients with early to mild Alzheimer’s. We plan to recruit patients for this study in North America and possibly internationally, and to power the trial to detect efficacy on ADAS-cog.
ALZ-801 Study in APOE4/4 with Early to Mild Alzheimer’s
Study Designed to be Consistent with New Draft FDA & EMA Guidances
APOE4/4 Initial Study Population for ALZ-801 Program
Targeting Homogeneous AD Population for Phase 3 & First Approval
- ALZ-801 well differentiated from leading AD programs
- Mechanism of action targets primary driver of disease: toxic soluble amyloid oligomers
- Administration of ALZ-801 enhances anti-Aβ oligomer protection though metabolite 3-SPA that is naturally present in the brain
- Clinical dose adequately inhibits amyloid oligomer formation in human brain
- ALZ-801 formulated in well-absorbed oral pill
- Favorable safety in 1,600 AD patients, with no cases of brain edema on treatment
- Prior analyses in accurately diagnosed APOE4/4 patients demonstrate clinical efficacy
- Almost all APOE4/4 AD patients (98%) have brain amyloid on imaging
- Most homogenous amyloid driven pathology among AD patients
- Faster rate of disease progression & clinical decline
Alzheon publications: Abushakra (2017) J Prev Alz Dis; Hey (2017) Clin Pharmacokinet; Hey (2018) CNS Drugs
ALZ-801 Program Builds on Recent Learnings
We believe ALZ-801 has the potential to be differentiated from other emerging therapies targeting Alzheimer’s disease pathology due to its novel mechanism of action, oral mode of administration, potential efficacy in a genetically-targeted population. If our development program is successful and ALZ-801 is approved, we believe it has the potential to be among the first drugs to intervene in an underlying mechanism of Alzheimer’s disease.
| Problem | Lessons from Other Anti-Amyloid Agents | Advantage of ALZ-801 |
|---|---|---|
| Lack of inhibition of oligomers | Lack or insufficient inhibition of amyloid oligomers | Full inhibition of amyloid oligomers |
| Lack of target engagement | Plaque lowering on amyloid PET imaging | CSF amyloid reduction & preservation of brain volume |
| Poor brain penetration | ~1% for antibodies | ~40% |
| Poorly defined patient population | All-comer Alzheimer’s patients | Genetically-defined high risk Alzheimer’s patients |
| Lack of efficacy | Lack of alignment of mechanism with clinical efficacy | Mechanism translates to potential efficacy & clinical dose |
| Brain swelling side effects | At risk | None observed |