Presentations Highlight Recent Discovery of Inhibition of Formation of Toxic Beta Amyloid Oligomers and New Insights for Precision Medicine Approach for ALZ-801 Targeting APOE4 Carriers

FRAMINGHAM, Mass., July 17, 2017 – Alzheon, Inc., a clinical stage biopharmaceutical company focused on developing new medicines for patients suffering from Alzheimer’s disease and other neurological and psychiatric disorders, today announced data from the company’s three presentations at the Alzheimer’s Association International Conference (AAIC) to be held in London on July 16-20, 2017.

These presentations at AAIC represent the convergence of research efforts by Alzheon for ALZ-801, an anti-amyloid drug candidate that is an optimized prodrug of tramiprosate, with R&D findings that range from the discovery of a novel molecular mechanism of action, to long-term clinical efficacy data in patients with Alzheimer’s disease (AD).  Together, these analyses confirm a Precision Medicine approach with ALZ-801 by showing the clinical efficacy of tramiprosate in a genetically-defined subpopulation of patients with apolipoprotein E4 (APOE4) genotype, and aligning the role of APOE4 and beta amyloid pathology in AD, through the following key observations:

  • The largest efficacy signal of tramiprosate was shown in patients with two APOE4 alleles (APOE4/4 homozygotes) with Mild AD, in Phase 3 studies of oral tramiprosate;
  • Tramiprosate inhibits formation of beta amyloid oligomers at clinically relevant concentrations achieved in AD patients, through a novel mechanism of ‘enveloping’ the native amyloid peptide;
  • Soluble toxic beta amyloid oligomers play a key role early in the AD process, and this is intensified in APOE4/4 patients who have a higher burden of oligomers compared to APOE4 non-carriers.

“All of our research and insights have brought us to the point where we can confirm how ALZ-801 blocks Alzheimer’s amyloid pathology, and confidently pursue our goal of directing an oral medicine for the Alzheimer’s patients who will most benefit from the treatment,” said Martin Tolar, MD, PhD, Founder, President and CEO of Alzheon.  “Our efforts have spanned the continuum – from understanding the molecular mechanism of action of inhibiting oligomers, to revealing clinical efficacy in the genetically-defined population of APOE4/4 homozygotes, and showing strong effects in those patients with Mild disease – enabling us to understand how our treatment works.  Together, these observations position us to developing ALZ-801 along a highly focused and targeted clinical path, as we move toward a pivotal study as quickly as possible to address the urgent needs of patients.”

Alzheon will make two presentations at AAIC related to the novel beta amyloid anti-oligomer mechanism of action of ALZ-801.  The presentations highlight Alzheon’s discovery of the novel molecular mechanism of action of tramiprosate, the active agent in the optimized prodrug ALZ-801, blocking formation of toxic amyloid oligomers, which play a key role early in the Alzheimer’s disease process.  At the AAIC, Alzheon will expand on its recently-published mechanism of action of tramiprosate, demonstrating that tramiprosate acts through a novel enveloping mechanism to inhibit beta amyloid monomer aggregation and formation of toxic amyloid oligomers at clinically relevant doses.1  Further results demonstrated that the concentrations of tramiprosate in the brain were sufficient to elicit the full inhibition of oligomer formation, and confirmed the dose selection of ALZ-801 for the confirmatory Phase 3 program planned in AD patients.

Alzheon will also make a presentation on new clinical analyses supporting the company’s Precision Medicine clinical program for ALZ-801, further expanding on Alzheon’s body of research from previous tramiprosate Phase 3 studies showing an APOE4 gene dose effect, with the largest clinical benefit observed in APOE4/4 homozygotes.2  Alzheon will present details from the recently-published analyses of Phase 3 data that showed the largest efficacy signals of tramiprosate in APOE4/4 homozygous patients with Mild Alzheimer’s disease.3   In addition, at the AAIC, Alzheon will present analyses of efficacy and safety in APOE4/4 homozygotes with AD from the Phase 3 studies who continued into an Extension Study for an additional 52 weeks, when all subjects received high dose of tramiprosate.  Results from the Extension Study showed that APOE4/4 AD subjects who received the high dose of tramiprosate over 130 weeks, showed persistent efficacy compared to subjects who had a delayed start on active drug (i.e., initial placebo-treated subjects), suggesting a disease-modification effect.

Detailed data from the AAIC poster presentations are available in the presentation section of Alzheon’s website:

About Alzheon

Alzheon, Inc. is committed to developing innovative medicines by directly addressing the underlying pathology of devastating neurodegenerative disorders.  Our lead Alzheimer’s clinical candidate, ALZ-801, is a Phase 3-ready, first-in-class, small molecule oral inhibitor of amyloid aggregation and neurotoxicity – hallmarks of Alzheimer’s disease.  ALZ-801 is a novel prodrug that builds on the safety and efficacy profile of the active compound tramiprosate, which has been evaluated in clinical trials involving over 2,000 Alzheimer’s patients.  Our clinical expertise and technology platform is focused on developing drug candidates using a Precision Medicine approach based on individual genetic and biological information to advance therapies with the greatest impact for patients.

  1. Kocis et al: Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data, CNS Drugs, June 2017; 31(6): 495-509.
  2. Abushakra et al:Clinical Benefits of Tramiprosate in Alzheimer’s Disease Are Associated with Higher Number of APOE4 Alleles: The “APOE4 Gene-Dose Effect” Journal of Prevention of Alzheimer’s Disease, October 2016; 3(4): 219-228. jpreventionalzheimer.com24Oct2016
  3. Abushakra et al: Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer’s Disease Suggest Disease Modification Potential, Journal of Prevention of Alzheimer’s Disease, published online June 22, 2017. jpreventionalzheimers.com22June2017

Kathryn Morris
The Yates Network