FRAMINGHAM, Mass.--(BUSINESS WIRE)--Alzheon, Inc., a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced that Martin Tolar, MD, PhD, the company’s Founder, President and Chief Executive Officer will present at the H.C. Wainwright Bioconnect Conference on January 10th. The presentation will be available live on-demand from 1:00 PM EST on January 10th until the end of the conference on January 13th.
The conference will provide an opportunity for investors to engage in one-on-one meetings with Dr. Tolar and the Alzheon team, and to hear about recent developments in Alzheon’s progress towards a potential New Drug Application for anti-amyloid treatment ALZ-801 (valiltramiprosate), an oral agent being evaluated in Alzheon’s pivotal APOLLOE4 Phase 3 trial, which started enrolling patients in June of 2021, and the Phase 2 biomarker trial, which completed full enrollment last summer. Dr. Tolar will also discuss upcoming data readouts and inflection points for Alzheon’s product platform in 2022.
“2021 was a groundbreaking year for the entire Alzheimer’s space and provided robust validation for Alzheon’s precision medicine approach of targeting toxic amyloid oligomers initially in patients genetically predisposed for the disease. Our data and results from trials with antibodies continue to show superior efficacy of anti-amyloid treatments in patients with the APOE4 genotype, which leads to an increase in concentration of neurotoxic amyloid oligomers in the brain, as well as a higher risk and faster progression of Alzheimer’s,” said Martin Tolar, MD, PhD, Alzheon Founder, President, and CEO. “Alzheon has developed a well-differentiated approach to both treatment and prevention of Alzheimer’s disease with the small molecule oral tablet, ALZ-801/valiltramiprosate, which acts on the same pathway as anti-amyloid antibodies but works upstream to prevent the formation of neurotoxic soluble amyloid oligomers, without impacting the insoluble plaque. ALZ-801 is, therefore, in a class of its own as a small-molecule oral drug that has shown potential for robust efficacy with a favorable safety profile, by avoiding the vascular complications of brain edema and microbleeds seen with infusions of plaque-clearing anti-amyloid antibodies. In 2022, our focus will be on biomarker data readouts from the Phase 2 trial and completion of enrollment in the pivotal Phase 3 APOLLOE4 study, which positions ALZ-801 tablet to potentially become the first oral, disease-modifying agent for Alzheimer’s patients and healthy individuals at risk for the disease.”
Dr. Tolar’s presentation will provide an overview of Alzheon’s ongoing Phase 3 APOLLOE4 program with the lead oral drug candidate ALZ-801, as well as updates from the Phase 2 biomarker study and developments in Alzheon’s product platform we expect in 2022 and beyond. ALZ-801 is a small molecule drug that blocks the formation of neurotoxic amyloid oligomers and has shown potential for robust efficacy and favorable safety in the highest-risk Alzheimer’s population – patients with two copies of the apolipoprotein ε4 allele (APOE4/4) – the focus of Alzheon’s pivotal Phase 3 APOLLOE4 trial, thereby maximizing the likelihood of success of the study. Last year, Alzheon scientists reported novel biomarker data and insights from our Phase 2 study with oral tablet ALZ-801, demonstrating the clear distinction between homozygous and heterozygous APOE4 patients with Early AD. This data helps explain the differential efficacy and safety outcomes in these populations in clinical studies with anti-amyloid agents and validates the selection of homozygous APOE4/4 patient population for the ongoing ALZ-801 APOLLOE4 Phase 3 study.
With endorsement from the National Institute on Aging in the form of an unprecedented $47M grant to fund the APOLLOE4 Phase 3 study with ALZ-801, Alzheon’s drug candidate is well positioned to become one of the first potential disease-modifying treatments approved for slowing and even preventing cognitive decline in Alzheimer’s patients. Pioneering a precision medicine approach in Alzheimer’s, the APOLLOE4 Phase 3 trial is enrolling the highest-risk APOE4/4 AD patients and incorporates the latest biomarkers to track patient benefits – phosphorylated tau in cerebrospinal fluid and blood, synaptic and inflammatory biomarkers, hippocampal volume, and cortical thickness measures, along with the gold-standard primary clinical endpoint, ADAS-Cog13 (Alzheimer's Disease Assessment Scale-Cognitive Subscale).
“New data from anti-amyloid programs continue to support Alzheon discoveries and publications proving that the degree of amyloid oligomer selectivity is the key factor that, together with pharmacokinetic properties, determines the magnitude of the benefit and risk profile for each anti-amyloid agent,” said Dr. Tolar. “While effects on neurotoxic soluble amyloid oligomers correlate with clinical benefit, the clearance of insoluble amyloid plaque from vessel walls by anti-amyloid antibodies leads to the side effects of vasogenic edema and brain bleeds due to small vessel injury at the clinically efficacious dose. ALZ-801 is an oral drug that does not interact with amyloid plaque and, therefore, is not associated with the risk of vasogenic edema, making the ALZ-801 treatment much more accessible to patients, with the potential to have a significant impact around the world.”
About ALZ-801
ALZ-801 is an oral agent in Phase 3 development as a potentially disease modifying treatment for AD.1,3 In mechanism of action studies, ALZ-801 has been shown to fully inhibit the formation of neurotoxic soluble amyloid oligomers at the Phase 3 clinical dose.5,6 ALZ-801 is an optimized prodrug of tramiprosate that has shown promising results in analyses of Phase 3 clinical data,7,9 and has a novel anti-amyloid oligomer mechanism of action.5,8 ALZ-801 received Fast Track designation from the U.S. Food and Drug Administration in 2017. The clinical data for ALZ-801 and its active agent, tramiprosate indicate long-term clinical efficacy in AD patients with the APOE4 genotype and a favorable safety profile.5–7,9 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 of cognitive symptoms and progression of AD.1–4 The cognitive improvements observed in the tramiprosate Phase 3 studies may also be attributed in part to the therapeutic effects of 3-sulfopropanoic acid (3-SPA), an endogenous anti-oligomer substance found in the human brain discovered by Alzheon scientists that, like tramiprosate, inhibits formation of toxic amyloid oligomers.5 3-SPA is the primary metabolite of ALZ-801 and its discovery helps explain the beneficial pharmaceutical attributes of ALZ-801, including favorable safety profile, high selectivity for amyloid, and excellent brain penetration.3,5,6 ALZ-801 treatment increases levels of 3-SPA in the brain and augments the body’s natural mechanism to inhibit formation of toxic amyloid oligomers.5,6 The initial Phase 3 program for ALZ-801 is focusing on Early AD patients with the APOE4/4 genotype, with future expansion to AD treatment and prevention in patients carrying one copy of the APOE4 gene.1–4
ALZ-801 APOLLOE4 Phase 3 Study
An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This ongoing study 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 the APOE4/4 genotype, who constitute approximately 15% of Alzheimer's patients. This is a double-blind, randomized trial comparing one dose of oral ALZ-801 to placebo treatment over 78 weeks. The APOLLOE4 trial is supported by a $47 million grant from the National Institute on Aging.
ALZ-801 Phase 2 Biomarker Study
Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease (NCT04693520): This ongoing study is designed to evaluate the effects of 265 mg twice daily oral dose of ALZ-801 on biomarkers of Alzheimer's pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotypes, who constitute 65-70% of Alzheimer's patients. The study also includes evaluation of clinical efficacy, safety, and tolerability of ALZ-801 over 104 weeks of treatment and will evaluate the extended pharmacokinetic profile of ALZ-801 over 8 hours in 24 subjects after 65 weeks of treatment.
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 devastating neurodegenerative disorders. Our lead Alzheimer’s clinical candidate, ALZ-801, is an oral agent in Phase 3 development as a potentially disease modifying treatment for AD. ALZ-801 is an oral small molecule prodrug of tramiprosate that fully blocks formation of neurotoxic soluble amyloid oligomers in the brain. ALZ-801 is an easy-to-take tablet that builds on the safety and efficacy profile of its 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 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.
