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 Aβ oligomer formation, a key driver of AD.
ALZ-801 was developed to improve gastrointestinal tolerability and the PK 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 favorable safety, 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 PK profile, and through our focus on APOE4/4 homozygous patients who carry a higher Aβ burden, believe that patients will be less likely to be misdiagnosed with AD.
ALZ-801 Biological Pathway
In October 2017, ALZ-801 was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of AD. We plan to initiate a Phase 3 trial for ALZ-801 in APOE4/4 homozygous patients with mild AD in 2018. This trial will be an 18-month, double-blind, placebo-controlled Phase 3 trial in APOE4/4 homozygous patients with mild AD. We plan to recruit patients for this study in North America and internationally, and to power the trial to detect efficacy on the co-primary outcomes of ADAS-cog and CDR-SB.
ALZ-801 Phase 3 Study in APOE4/4 with Mild AD
FDA-Accepted Study Design in APOE4/4 AD Patients
Our Program Builds on Recent Learnings
We believe ALZ-801 has the potential to be differentiated from other emerging therapies targeting AD pathology due to its novel mechanism of action, oral mode of administration, potential efficacy in a genetically-targeted population and observed favorable safety profile. 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 AD.
| Problem | Advantage of ALZ-801 | Lessons from Other Anti-Amyloid Agents |
|---|---|---|
| Efficacy data not supported | MOA translates to potential clinical efficacy target dose |
Lack of alignment of MOA with clinical data ( except aducanumab ) |
| Lack of inhibition of Aβ oligomers | Inhibits formation of amyloid oligomers | Insufficient targeting of Aβ oligomers ( except aducanumab ) |
| Poor brain penetration | ~40% | Low penetration for antibodies |
| Lack of target engagement | CSF Aβ42 reduction & decrease in hippocampal atrophy |
Plaque lowering on PET imaging |
| Poorly defined patient population | APOE4/4 Mild AD patients | APOE4 carriers & non-carriers |
| Development of vasogenic edema | None observed | At risk |