Results Support Pivotal Phase 3 Development of ALZ-801 in Genetically-Defined APOE4/4 Patients and Further Expansion to Additional Alzheimer’s Populations

FRAMINGHAM, Mass., October 24, 2017 – Alzheon, Inc., today announced the publication of clinical results demonstrating that ALZ-801 achieved levels of therapeutic efficacy with favorable safety and tolerability profile for use as an orally-administered medicine for the treatment of Alzheimer’s disease (AD). ALZ-801 is an oral, amyloid-targeted therapy that blocks the formation of toxic beta amyloid oligomers associated with the development and progression of AD.

These data establish the clinical dose of ALZ-801 of 265 mg administered orally twice daily, which correlates with therapeutic levels of the active agent tramiprosate that showed positive cognitive and functional improvements in Alzheimer’s patients with apolipoprotein E4 (APOE4) genotype. The manuscript titled “Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for Treatment of Alzheimer’s Disease” is featured in the advanced online publication of the journal Clinical Pharmacokinetics, and the paper is available through open access at

The published data support the Phase 3 development of ALZ-801, and build on the novel research findings demonstrating ALZ-801’s molecular mechanism of action and projected efficacy in AD patients. Efficacy analyses from previous studies of ALZ-801’s active agent, tramiprosate, demonstrated a gene-dose response, with the largest efficacy signals shown in patients with two APOE4 alleles (APOE4/4 homozygotes) with Mild Alzheimer’s disease.1 Based on these results, Alzheon plans a pivotal Phase 3 clinical study with ALZ-801, applying a Precision Medicine approach in a genetically-defined population of AD patients who are APOE4/4 homozygotes, followed by further expansion to evaluate ALZ-801 in additional populations of AD patients.

“These published results with ALZ-801 come at a time when we are seeing a convergence of new insights on how amyloid-targeted therapies can be optimized to treat Alzheimer’s disease patients,” said Dr. Anton Porsteinsson, Professor of Psychiatry and Neurology and Director of the Alzheimer’s Disease Care, Research and Education Program at University of Rochester School of Medicine and Dentistry. “Alzheon has led a path toward new understanding of amyloid biology and pathogenesis, from recent studies on molecular mechanisms of action, to translational clinical analyses, and ALZ-801 patient data. These observations position us better to develop breakthrough therapies for Alzheimer’s and to choose populations most likely to respond to treatment.”

“Against the backdrop of the challenges in drug development for neurodegenerative disorders, we are pioneering a targeted, higher probability path for developing ALZ-801 for Alzheimer’s disease patients. With ALZ-801, we are pursuing a Precision Medicine approach to focus first on a genetically-defined subset of high-risk Alzheimer’s patients with the APOE4 genotype, who have shown the largest response to our lead molecule. However, our work to help patients will not stop there, as we see broad application for ALZ-801 as a potential disease-modifying treatment for many AD patient populations,” said Martin Tolar, MD, PhD, Founder, President and CEO of Alzheon.  “We are moving toward pivotal Phase 3 study for ALZ-801 as rapidly as possible, to advance ALZ-801 as a potentially transformative Alzheimer’s medicine to address the urgent needs of Alzheimer’s patients.”

The observed APOE4 gene-dose effects of ALZ-801’s active agent are consistent with the prevalence of amyloid pathology as well as diagnostic accuracy in AD patients. Amyloid imaging in AD clinical trials has shown the highest prevalence of positive amyloid scans in APOE4/4 homozygotes (>95%), and the lowest prevalence in APOE4 non-carriers (40%).2 As one of the few orally-available drug agents that can block the aggregation of beta amyloid monomers into toxic soluble oligomers,3 ALZ-801 is a prospective disease modifying drug for Alzheimer’s disease with potential utility for a wide range of AD patient populations.

“ALZ-801 represents a new category of agents with disease-modifying potential:  an oral, well-tolerated tablet that targets the underlying amyloid pathology in Alzheimer’s. Furthermore, we succeeded to substantially optimize pharmaceutical profile of ALZ-801, achieving excellent pharmacokinetics, as well as favorable tolerability and safety,” said John Hey, PhD, Chief Scientific Officer of Alzheon. “Based on our robust clinical efficacy data, we are confident and excited to initiate the pivotal development of ALZ-801, as the first drug in a new class of medicines that intervene in the formation of neurotoxic oligomers, a landmark treatment that offers potential to slow the progression of Alzheimer’s disease as well as other currently untreatable neurological disorders.”

About ALZ-801

ALZ-801 is a novel, oral anti-amyloid drug candidate that is an optimized prodrug of tramiprosate, which has shown promising results in analyses of clinical data and therapeutic mechanism of action. This includes the discovery of its novel molecular mechanism of action blocking the formation of toxic amyloid oligomers3 associated with the development and progression of AD.4  The clinical data for ALZ-801 and its active agent, tramiprosate, suggest long-term clinical efficacy in AD patients with the APOE4 genotype, along with a favorable safety profile.1 The initial Phase 3 program for ALZ-801 will focus on patients with the homozygous APOE4/4 genotype at the Mild stage of AD, with the potential for future expansion to additional Alzheimer’s populations.

About Apolipoprotein E

Apolipoprotein E, or APOE, is a gene that provides a predictive window into an individual’s Alzheimer’s disease prognosis. In the brain, apolipoprotein E helps shuttle cholesterol to neurons to support their normal function. There are three forms, or alleles, of the APOE gene, called ε2, ε3 and ε4. The ε4 allele has been found to correlate with high risk and earlier onset of Alzheimer’s disease. It is estimated that up to 65% of all AD patients in the U.S. are carriers of at least one APOE4 allele, and that 10-15% of the AD population, or approximately 560,000 individuals in the U.S., are APOE4/4 homozygotes.5 APOE4 carriers – and more considerably APOE4/4 homozygotes – show faster rates of cognitive decline, at pre-symptomatic, early and dementia stages of the disease.6 In addition, APOE4 carriers, in comparison to non-carriers, show a higher and faster accumulation of amyloid pathology, including soluble amyloid oligomers.7

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 Abushakra et al. 2016, Abushakra et al. 2017
2 Sperling et al. 2011
3 Kocis et al. 2017
4 Esparza et al. 2013, Lesne et al. 2012
5 Ward et al. 2012
6 Caselli et al. 2009; Martins et al. 2005
7 Grimmer et al. 2010, Hashimoto et al. 2012

Kathryn Morris
The Yates Network