Fully Enrolled Pivotal APOLLOE4 Phase 3 Trial in Early Alzheimer’s Patients on Track for Topline Data Readout and Initiation of NDA Submission in 2024

ALZ-801 Tablet Inhibits Formation of Soluble Toxic Amyloid Aggregates and Acts Upstream from All Late-Stage Amyloid Targeting Treatments

Robust and Sustained P-tau181 Reduction in Plasma, Combined with Preservation of Brain Volume and Positive Correlations with Cognitive Effects, Reinforces Potential of ALZ-801 to Slow Alzheimer’s Disease Progression

ALZ-801 Safety Results Remain Favorable & Consistent with Prior Formulation’s Data Resulting in Safety Database of Over 3,000 AD Patients, Showing no Increased Risk of Vasogenic Brain Edema

FRAMINGHAM, Mass., February 27, 2024 — Alzheon, Inc., a clinical-stage biopharmaceutical company developing a portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer’s disease (AD) and related neurodegenerative disorders, today announced its participation in the upcoming International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD) in Lisbon, Portugal from March 5–9, 2024.

“The new treatment landscape for Alzheimer’s disease is beginning to take shape, and Alzheon’s simplified approach has an opportunity to transform the standard of care and improve access to treatment for Alzheimer’s patients. ALZ-801’s efficacy data and favorable safety profile, showing no increased risk of vasogenic edema, underscore the differentiated clinical profile of our treatment,” said Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon. “The growing body of evidence continues to support ALZ-801’s potential as the first oral anti-amyloid disease modifying therapy for Alzheimer’s disease, and we are excited about the potential of ALZ-801 to improve access to treatment for patients around the world. Results from our pivotal APOLLOE4 Phase 3 trial will set the stage for the potential NDA filing this year and commercial launch in 2025.”

Alzheon presentations include two posters and two symposium presentations. Details of the presentations are as follows:

Poster: APOLLOE4 Phase 3 Trial of Oral Anti-Amyloid Agent ALZ-801/Valiltramiprosate in APOE4/4 Early Alzheimer’s Patients: Study Design and Baseline Characteristics

  • Presenter: Earvin Liang, PhD, Vice President of Clinical Development, Alzheon, Inc.
  • Date & Time: Poster Shift 1 – Wednesday, March 6 at 09:00 a.m. CET to Thursday, March 7 at 18:00 p.m. CET

Poster: APOE4/4 Homozygous Alzheimer’s Patients with Comorbid Cerebral Amyloid Angiopathy: Baseline Analyses from Phase 3 Trial of Oral Anti-Amyloid Agent ALZ-801/Valiltramiprosate

  • Presenter: Aidan Power, MB, MSc, MRCPsych, Chief Development Officer, Alzheon, Inc.
  • Date & Time: Poster Shift 2 – Friday, March 8 at 09:00 a.m. CET to Saturday, March 9 at 18:00 p.m. CET

Symposium Presentation: 104-Week Effects of ALZ-801/Valiltramiprosate on Plasma, MRI Biomarkers and Cognition Support Disease Modification in APOE4 Carriers with Early Alzheimer’s Disease

  • Presenter: John Hey, PhD, Chief Scientific Officer, Alzheon, Inc.
  • Session Name: 6730 – Translational Treatment Strategies and New Targets (ID 105)
  • Location: Auditorium V
  • Lecture Date & Time: Saturday, March 9 at 09:25-09:40 a.m. CET

Symposium Presentation: Use of ADNI-1 Cohort as Comparator-Arm In ALZ-801/Valiltramiprosate Phase 2 Study of APOE4 Carriers with Alzheimer’s Disease: Regulatory Basis and Statistical Considerations

  • Presenter: Larry Shen, PhD, Vice President & Head of Biometrics, Pharmapace, Unit of WuXi AppTec
  • Session Name: 6980 – Neurodegeneration: Diverse Mechanisms Fluid Biomarkers and Imaging (ID 431)
  • Location: Auditorium III + IV
  • Lecture Date & Time: Saturday, March 9 at 18:40-18:55 p.m. CET

“We have now entered the era of disease modification in Alzheimer’s disease, and later this year we are expecting the readout of our pivotal APOLLOE4 Phase 3 trial evaluating oral tablet ALZ-801/valiltramiprosate. If the results of our study are positive, we will be moving quickly to bring an oral option to Alzheimer’s patients and their families,” said John Hey, PhD, Chief Scientific Officer. “The magnitude of p-tau181 biomarker reduction in plasma compared to that of plaque-clearing anti-amyloid antibodies, combined with preservation of brain hippocampal volume and its robust positive correlations with cognitive benefits, reinforces our conviction that ALZ-801 has the potential to disrupt the Alzheimer’s treatment paradigm by slowing the progression of this debilitating disease.”

About ALZ-801

ALZ-801/valiltramiprosate is an investigational oral agent in Phase 3 development as a potentially disease modifying treatment for AD.1,3 ALZ‑801 is designed to block the formation of neurotoxic soluble beta amyloid oligomers causing cognitive decline in Alzheimer’s patients. In mechanism of action studies, ALZ-801 has fully inhibited the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical dose.5,6 ALZ‑801 acts through a novel enveloping molecular mechanism of action to fully block formation of neurotoxic soluble amyloid oligomers in the human brain7 associated with the onset and progression of cognitive decline in AD patients.1–4 ALZ-801 received Fast Track designation from the U.S. Food and Drug Administration in 2017 for Alzheimer’s disease. In clinical trials, ALZ-801 has shown favorable safety results.5–7,9 The initial Phase 3 program for ALZ-801 is focusing on Early AD patients with the APOE4/4 genotype, with potential future program expansion to AD treatment and prevention in patients carrying one copy of the APOE4 gene and noncarriers.1–4

ALZ-801 Phase 2 Biomarker Trial

Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer’s Disease (NCT04693520): This ongoing trial is designed to evaluate the effects of 265 mg twice daily oral dose of ALZ-801 on biomarkers of AD pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotype and constitute 65-70% of Alzheimer’s patients. The trial also includes evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of ALZ-801 over 104 weeks of treatment. An ongoing long-term extension of the trial evaluates ALZ-801 for an additional 52 weeks of treatment for a total of 156 weeks.

ALZ-801 APOLLOE4 Phase 3 Trial

An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early Alzheimer’s Disease Subjects (NCT04770220): This ongoing trial is designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of ALZ-801 in Early AD subjects with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer’s patients. This is a double-blind, randomized trial comparing oral ALZ-801 to placebo treatment over 78 weeks. The APOLLOE4 trial is supported by a $51 million grant from the National Institute on Aging.

About Alzheon

Alzheon, Inc. is a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer’s disease and other neurodegenerative disorders. We are committed to developing innovative medicines by directly addressing the underlying pathology of neurodegeneration. Our lead Alzheimer’s clinical candidate, ALZ-801/valiltramiprosate, is an oral agent in Phase 3 development as a potentially disease modifying treatment for AD. ALZ-801 is an oral small molecule that has been observed to fully block the formation of neurotoxic soluble amyloid oligomers in preclinical tests. Our clinical expertise and technology platform are focused on developing drug candidates and diagnostic assays using a precision medicine approach based on individual genetic and biomarker information to advance therapies with the greatest impact for patients.

Alzheon Scientific Publications

1 Tolar M, et al: Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression, International Journal of Molecular Sciences, 2021; 22, 6355.

2 Abushakra S, et al: APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease Show Accelerated Hippocampal Atrophy and Cortical Thinning that Correlates with Cognitive Decline, Alzheimer’s & Dementia, 2020; 6: e12117.

3 Tolar M, et al: Aducanumab, Gantenerumab, BAN2401, and ALZ-801—the First Wave of Amyloid-Targeting Drugs for Alzheimer’s Disease with Potential for Near Term Approval, Alzheimer’s Research & Therapy, 2020; 12: 95.

4 Tolar M, et al: The Path Forward in Alzheimer’s Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer’s & Dementia, 2019; 1-8.

5 Hey JA, et al: Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain, CNS Drugs, 2018; 32(9): 849-861.

6 Hey JA, et al: Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer’s Disease, Clinical Pharmacokinetics, 2018; 57(3): 315–333.

7 Abushakra S, 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, 2017; 4(3): 149-156.

8 Kocis P, 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, 2017; 31(6): 495-509.

9 Abushakra S, 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, 2016; 3(4): 219-228.

Media Contact
Glenn Pauly, Alzheon, Inc.
508.861.7709
media@alzheon.com

Investor Contact
Ken Mace, Alzheon, Inc.
508.861.7709
investor@alzheon.com