Alzheon to Present Industry-Leading Biomarker, Brain Preservation, and Clinical Effects with Oral ALZ-801 (Valiltramiprosate) at 15th Annual Clinical Trials in Alzheimer’s Disease Conference

New Results Position ALZ-801 to Potentially Become the First Oral Agent that Can Slow or Even Stop and Prevent Alzheimer’s Pathology in Patients and Healthy Individuals at Risk for the Disease

Several-Fold Greater Reduction on P-tau₁₈₁ Compared to Plaque-Clearing Antibodies and Unprecedented Preservation of Hippocampal Volume Validate Superior Clinical Benefits from Prior Studies in Alzheimer’s Patients

Significant Improvement from Baseline on Memory Tests at 3 and 6 Months, and Disease Stabilization Above Baseline at 1-Year Timepoint, to be Further Confirmed in Ongoing APOLLOE4 Phase 3 Trial

Safety profile in ALZ-801 Studies Remains Favorable & Consistent with Prior Data in Over 2,000 AD Patients, with no Evidence of Vasogenic Brain Edema

FRAMINGHAM, Mass., November 22, 2022–(BUSINESS WIRE)–Alzheon, Inc., a clinical-stage biopharmaceutical firm growing a broad portfolio of product candidates and diagnostic assays for sufferers affected by Alzheimer’s illness (AD) and different neurodegenerative issues, right now introduced that it will likely be presenting new medical trial knowledge on the 15^th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference to be held from November 29 – December 2, 2022 in San Francisco, CA, USA.

Alzheon Chief Medical Officer, Susan Abushakra, MD, will give a podium presentation on the CTAD convention on Friday, December 2, 2022, at 11:45 a.m. PT or 2:45 p.m. ET. This oral presentation will likely be included within the Focus Session: Interim or Preliminary Data and Study Design.

The CTAD presentation: Significant Effects of Oral ALZ-801 on Plasma Biomarkers of Alzheimer’s Disease: 12-Month Interim Analysis of Phase 2 Biomarker Study in APOE4 Carriers with Early AD, will present a possibility to listen to from Dr. Abushakra as she discusses the statistically important and clinically related discount in biomarkers of neurodegeneration, sturdy preservation of mind quantity, and constructive reminiscence results in Alzheimer’s sufferers following 12 months of therapy with investigational agent ALZ-801 within the totally enrolled Phase 2 biomarker trial. Dr. Abushakra may also present an replace on the continued pivotal APOLLOE4 Phase 3 trial evaluating ALZ-801 oral pill in Alzheimer’s sufferers, and the trail to New Drug Application (NDA) for the ALZ-801 (valiltramiprosate) program.

“Alzheon has pioneered precision drugs in Alzheimer’s illness by focusing on neurotoxic amyloid oligomers, and now very promising biomarker, imaging, and medical knowledge with ALZ-801 present further help for this strategy. Across many trials of anti-amyloid therapies, p-tau₁₈₁ has emerged as a constant plasma biomarker that correlates with medical profit. The several-fold larger discount on the p-tau₁₈₁ biomarker in plasma in comparison with plaque-clearing anti-amyloid antibodies, mixed with preservation of mind hippocampal quantity and their constructive correlations with cognitive advantages, validate the illness modifying results of ALZ-801 in Alzheimer’s sufferers,” mentioned Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon. “Importantly, somewhat than slowing the cognitive decline of sufferers as seen in trials with different brokers, topics handled with ALZ-801 demonstrated cognitive enchancment from baseline standing on reminiscence checks and maintained their cognitive skills over 1 12 months of therapy. These well-differentiated outcomes mixed with a good security profile exhibiting no occasions of vasogenic edema, place ALZ-801 to probably turn out to be the primary oral agent that may sluggish and even cease and stop Alzheimer’s pathology in sufferers and wholesome people in danger for the illness.”

ALZ-801 (valiltramiprosate) is an oral agent in Phase 3 development as a probably illness modifying therapy for AD that blocks formation of neurotoxic soluble beta amyloid (Aβ) oligomers inflicting cognitive decline in Alzheimer’s sufferers. In mechanism of motion research, ALZ-801 totally inhibited the formation of amyloid oligomers on the Phase 3 medical dose. ALZ-801 has proven potential for sturdy efficacy within the highest-risk Alzheimer’s inhabitants – sufferers with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), and favorable security with no occasions of mind vasogenic edema seen in trials with plaque-clearing antibodies. This inhabitants is the main target of ongoing Alzheon’s pivotal Phase 3 APOLLOE4 trial and has the best chance of demonstrating profitable efficacy outcomes.

Alzheon’s Phase 2 AD biomarker examine (NCT04693520) enrolled 84 sufferers with Early AD, who carry both the APOE4/4 or APOE3/4 genotype and obtained oral ALZ-801 265 mg twice each day. All analyses of plasma biomarkers have been carried out on the laboratory of Professor Kaj Blennow at University of Gothenburg in Molndal, Sweden, and have been audited based on Good Laboratory Practice. A complete of 75 sufferers (imply age 69 years, 52% feminine) accomplished the Week 52 go to and have been included within the pre-specified evaluation. In this inhabitants, ALZ-801 demonstrated a big 41% discount from baseline in plasma p-tau₁₈₁ (p=0.016) at 52 weeks. ALZ-801 additionally considerably lowered the plasma p-tau₁₈₁/Aβ42 ratio by 37% at 52 weeks (p=0.032). Given the significance of p-tau₁₈₁and Aβ42 as biomarkers of core AD pathology, these outcomes help the illness modifying impact of ALZ-801 in Alzheimer’s sufferers.

“Trials with plaque-clearing antibodies proceed to help Alzheon science of focusing on neurotoxic soluble aggregates of beta amyloid, and our constructive outcomes characterize the most recent proof confirming the promise of ALZ-801, extending different key discoveries made by Alzheon scientists over the previous 9 years. The important impact on plasma p-tau₁₈₁, mixed with the hippocampal quantity preservation and medical stabilization after 12 months of therapy, validates the anti-amyloid oligomer motion of ALZ-801 in Alzheimer’s illness. This consistency throughout these three outcomes may be very encouraging and helps the rising illness modifying profile of ALZ-801 in Alzheimer’s sufferers,” mentioned Susan Abushakra, MD, Chief Medical Officer of Alzheon. “Alzheon has developed a well-differentiated strategy with small molecule ALZ-801, which acts upstream on the identical pathway as anti-amyloid antibodies, stopping the formation of neurotoxic soluble amyloid oligomers with out disrupting the insoluble plaque deposits in mind tissue and small vessels, thereby avoiding the vascular problems of mind edema and microbleeds seen with infusions of plaque-clearing antibodies. This knowledge highlights the potential security and efficacy benefits of ALZ-801 in comparison with plaque-clearing antibodies, whereas additionally providing a simplified affected person journey in the direction of an efficient therapy.”

With help from the National Institute on Aging within the type of a $47M grant to fund the APOLLOE4 Phase 3 study with ALZ-801, Alzheon’s drug candidate is nicely positioned to turn out to be one of many first disease-modifying therapies authorized for slowing and even stopping cognitive decline in Alzheimer’s sufferers. Pioneering a precision drugs strategy in Alzheimer’s, the APOLLOE4 Phase 3 trial is enrolling the highest-risk homozygous APOE4/4 AD sufferers and incorporates the most recent biomarker and volumetric MRI measures to trace affected person profit – ranges of p-tau₁₈₁and beta amyloid in plasma and cerebrospinal fluid, hippocampal quantity, and different volumetric mind measures, together with the gold-standard major medical endpoint, ADAS-Cog 13 (Alzheimer’s Disease Assessment Scale-Cognitive Subscale).

About ALZ-801
ALZ-801 (valiltramiprosate) is an investigational oral agent in Phase 3 development as a probably illness modifying therapy for AD.^1,3 In mechanism of motion research, ALZ-801 has been proven to completely inhibit the formation of neurotoxic soluble beta amyloid oligomers on the Phase 3 medical dose.^5,6 ALZ‑801 acts by a novel enveloping molecular mechanism of action to completely block formation of neurotoxic soluble amyloid oligomers within the human mind⁷ related to the onset of cognitive signs and development of AD.^1–4 ALZ-801 obtained Fast Track designation from the U.S. Food and Drug Administration in 2017. The medical knowledge for ALZ-801 and Alzheon’s security database point out a good security profile.^5–7,9 The preliminary Phase 3 program for ALZ-801 is specializing in Early AD sufferers with the APOE4/4 genotype, with future growth to AD therapy and prevention in sufferers carrying one copy of the APOE4 gene and noncarriers.^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 examine is designed to guage the efficacy, security, biomarker and imaging results of 265 mg twice each day oral dose of ALZ-801 in Early AD topics with the APOE4/4 genotype, who represent roughly 15% of Alzheimer’s sufferers. This is a double-blind, randomized trial evaluating oral ALZ-801 to placebo therapy 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 examine is designed to guage the results of 265 mg twice each day oral dose of ALZ-801 on biomarkers of Alzheimer’s pathology in topics with Early AD, who’ve both the APOE4/4 or APOE3/4 genotypes, who collectively represent 65-70% of Alzheimer’s sufferers. The examine additionally consists of analysis of medical efficacy, security, tolerability, and pharmacokinetic profile of ALZ-801 over 104 weeks of therapy.

About Alzheon
Alzheon, Inc. is a clinical-stage biopharmaceutical firm growing a broad portfolio of product candidates and diagnostic assays for sufferers affected by Alzheimer’s illness and different neurodegenerative issues. We are dedicated to growing modern medicines by instantly addressing the underlying pathology of neurodegeneration. Our lead Alzheimer’s medical candidate, ALZ-801 (valiltramiprosate), is an oral agent in Phase 3 development as a probably illness modifying therapy for AD. ALZ-801 is an oral small molecule that totally blocks formation of neurotoxic soluble amyloid oligomers within the mind. Our medical experience and expertise platform are targeted on growing drug candidates and diagnostic assays utilizing a precision medicine approach primarily based on particular person genetic and biomarker info to advance therapies with the best impression for sufferers.

Alzheon Scientific Publications
¹Tolar 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.
²Abushakra 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.
³Tolar 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.
⁴Tolar M, et al: The Path Forward in Alzheimer’s Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer’s & Dementia, 2019; 1-8.
⁵Hey 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.
⁶Hey 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.
⁷Abushakra 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.
⁸Kocis 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.
⁹Abushakra 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.