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Alzheon Presents New Findings in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease, Further Supporting Precision Medicine Approach and Planned Confirmatory Clinical Trial with ALZ-801


Presentation at the Alzheimer's Association International Conference
Details Patient Responder Analyses on Key Clinical Outcomes

 a clinical-stage biopharmaceutical company focused on
developing new medicines for patients suffering from Alzheimer's disease
(AD) and other neurological and psychiatric disorders, today announced
the upcoming presentation of data at the Alzheimer's Association
International Conference (AAIC) in Chicago on Wednesday, July 25th,

The presentation at the AAIC highlights new responder analyses that
focus on APOE4/4 homozygous patients with Mild AD at baseline, a
genetically-defined population that has previously shown the largest
clinical efficacy signals in the North American Phase 3 study of oral
tramiprosate.1,2 Tramiprosate is the active agent in ALZ-801,
Alzheon's Phase 3-ready drug candidate that is being developed as a
potential disease modifying treatment for Alzheimer's disease.

Large clinical benefit on both cognition and function have been observed
in APOE4/4 AD patients with Mild disease in the tramiprosate North
American study. In patients with Mild AD (MMSE 20 and above) treated
with the high dose of tramiprosate, 150 mg twice daily, the responder
analyses showed:

  • Significantly more patients remained cognitively stable over 78 weeks
    of treatment, based on measures of Alzheimer's Disease Assessment
    Scale-Cognitive Subscale (ADAS-cog): drug 57% vs. 20% for placebo;
  • Significantly more patients had minimal or no decline in function over
    78 weeks of treatment, based on measures of Disability Assessment for
    Dementia (DAD): drug 46% vs. 18% for placebo.

"Responder rates in APOE4/4 patients with Mild AD support meaningful
efficacy of tramiprosate in this population, and will help us design our
planned confirmatory studies with ALZ-801," said Susan Abushakra, MD,
Chief Medical Officer of Alzheon. "We continue to build on the body of
clinical evidence to support the development of ALZ-801, and we are
enthusiastic to initiate the pivotal program with ALZ-801 for
Alzheimer's patients in need of effective treatment."

These clinical data support Alzheon's precision medicine approach with
ALZ-801. The analyses further expand on Alzheon's previous findings from
the tramiprosate Phase 3 studies that showed the APOE4 gene dose effect,
with the largest clinical benefit in AD patients with two APOE4 alleles,
i.e. APOE4/4 homozygotes.1,2 This clinical profile is
consistent with the recently elucidated molecular mechanism of action,
where tramiprosate inhibits beta amyloid (Aβ) monomer aggregation and
formation of soluble toxic Aβ oligomers.3 These data are also
consistent with the positive clinical data from completed studies with
anti-amyloid antibodies aducanumab and BAN-2401 targeting soluble toxic
Aβ oligomers and proto-fibrils.

"This latest data presentation at AAIC strengthens the confidence in our
pioneering precision medicine approach for ALZ-801 in the
genetically-defined population of APOE4/4 homozygous patients with Mild
or Early Alzheimer's disease," said Martin Tolar, MD, PhD, Founder,
President and CEO of Alzheon. "Targeting soluble amyloid aggregates is
the only therapeutic approach to date that has shown a disease modifying
effect in Alzheimer's patients. We believe that our oral medicine may
provide a meaningful benefit to patients in need, and will continue our
targeted clinical approach to advance ALZ-801 as a breakthrough medicine
for the patients who will most benefit from the treatment."

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. ALZ-801 received Fast
Track designation by the U.S. Food and Drug Administration (FDA) in
October 2017. The clinical data for ALZ-8014 and its active
agent, tramiprosate, suggest long-term clinical efficacy in AD patients
with the APOE4 genotype, along with a favorable safety profile.1,2 ALZ-801
acts through a novel molecular
mechanism of action
 blocking the formation of toxic amyloid oligomers3 associated
with the development and progression of AD. 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
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. APOE4 carriers – and more considerably APOE4/4
homozygotes – show faster rates of cognitive decline, at
pre-symptomatic, early and dementia stages of the disease. In addition,
APOE4 carriers, in comparison to non-carriers, show a higher and faster
accumulation of amyloid pathology, including soluble amyloid oligomers.

About Alzheon
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
beta 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 are 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

Alzheon Publications:
et al. Journal of Prevention of Alzheimer's Disease, 2016

2 Abushakra
et al. Journal of Prevention of Alzheimer's Disease, 2017

et al. CNS Drugs, 2017

4 Hey
et al. Clinical Pharmacokinetics, 2018

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