valiltramiprosate (ALZ-801) / Alzheon, GSK - LARVOL DELTA

Naringenin as a dual-target modulator of RAGE-NF-κB signaling and Aβ fibrillization in Alzheimer's disease: integrated computational and experimental analyses. (PubMed, Front Pharmacol) - "At the Aβ fibril (PDB: 2MXU), NAR showed a superior docking score than ALZ-801 (valiltramiprosate), involving hydrogen bonding and π-π stacking with HIS_A14 (docking score: -8.098 kcal/mol)...Experimentally, NAR reduced Aβ42-induced NF-κB activation in RAGE-positive C6 cells, protected SH-SY5Y neurons from Aβ42 toxicity, and inhibited Aβ42 fibrillization in vitro, producing non-seeding aggregates consistent with impaired fibril formation, and attenuated rotenone-induced α-synuclein-associated cellular stress. Collectively, these findings support further investigation of NAR as a mechanistically plausible multi-target candidate for protein aggregation and RAGE-associated inflammatory signaling in neurodegenerative disease models."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Aβ42

Alzheon Announces Peer-Reviewed Publication Showing Oral Valiltramiprosate/ALZ-801 Achieves Sustained Plasma Biomarker Reductions Linked to Better Cognitive, Functional, and Brain Atrophy Outcomes in APOE4 Carriers with Early Alzheimer’s Disease (Yahoo Finance) - "In the overall Phase 3 population, baseline plasma p-tau217 levels were comparable between treatment arms and were significantly lower with valiltramiprosate than placebo at Weeks 26, 52, and 78 (all p<0.025). A similar effect was observed in the pre-specified MCI subgroup (p<0.05 at Weeks 52 and 78), while the Mild AD subgroup showed a numerical trend. In Phase 3 MCI subjects, baseline p-tau217 correlated significantly with baseline disease severity measures, including CDR-SB (r = 0.403, p = 0.002), hippocampal volume (r = −0.393, p = 0.002), and cortical thickness (r = −0.601, p<0.0001). In the valiltramiprosate arm, p-tau217 reductions at Week 78 correlated with less decline on ADAS-Cog13 (r = 0.276, p = 0.039) and CDR-SB (r = 0.377, p = 0.005), as well as less hippocampal atrophy (r = −0.353, p = 0.013)."

P3 data • Alzheimer's Disease

Phase 2 Findings Show Sustained Plasma Biomarker Reductions over Four Years, Supporting Valiltramiprosate's Long-Term Disease-Modifying Potential in APOE4 Carriers (Yahoo Finance) - "The primary outcome was the change from baseline in plasma p-tau181. The trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of valiltramiprosate over 104 weeks of treatment. A completed long-term extension of the trial evaluated the same dose of valiltramiprosate for an additional 104 weeks of treatment for a total of 208 weeks."

Biomarker • P2 data • Alzheimer's Disease

Plasma Biomarker Effects of Oral Valiltramiprosate/ALZ-801 in Early Alzheimer's Disease from Phase 3 and Phase 2 Trials: Analysis of Core Biomarkers and Correlations with Clinical and Neuroimaging Outcomes. (PubMed, Drugs) - P2, P3 | "Valiltramiprosate 265 mg BID produced early and sustained reductions in plasma p-tau217 and p-tau217/Aβ42 in APOE4 homozygotes and carriers with MCI. In Phase 3 MCI subjects, drug effects on both p-tau217 and NfL correlated significantly with clinical and vMRI benefits, and the two biomarkers were also significantly correlated with each other. These findings suggest that valiltramiprosate engages its central target, thereby reducing Aβ aggregation, tau hyperphosphorylation, and downstream neurodegeneration. The consistent associations of plasma p-tau217 and NfL changes with positive clinical and vMRI outcomes in MCI indicate that the pharmacodynamic biomarker response reflects broader disease-modifying biological effects and are consistent with valiltramiprosate's mode of action. Together with the previously reported favorable safety and absence of increased ARIA-E risk, these biomarker findings and their clinical correlations support the promising..."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Aβ42 • NEFL • Plasma NfL

A role for apolipoprotein E4 (ApoE4) in the pathogenesis of depressive symptoms and Alzheimer's disease. (PubMed, Biochem Pharmacol) - "We also explored specific therapeutic strategies targeting the pathological defects of ApoE4 that enhance synaptic resilience, and utilizing conformational modulating small molecules such as EZ-482 and ALZ-801 to treat depressive symptoms in early AD. Thus, these findings indicate that ApoE4 may influence the progression of depressive phenotypes through multiple pathological pathways, making it a promising therapeutic target for treating depression comorbid with early AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Depression • Mental Retardation • Metabolic Disorders • Psychiatry • APOE

Effects of Valiltramiprosate on Plasma P-tau217 and Select Pro-Inflammatory and Vascular Injury Biomarkers with the NULISA CNS Panel: Exploratory Analyses from the Phase 3 APOLLOE4 Trial in APOE4/4 Homozygotes with Early AD (CTAD 2026) - No abstract available

Biomarker • P3 data

The Oral Anti-Amyloid Agent Valiltramiprosate Reduces Spontaneous ARIA Rates in APOE4/4 Early AD Subjects: Results of the Phase 3 Placebo-Controlled APOLLOE4 Trial (CTAD 2026) - No abstract available

Clinical • P3 data

The Effects of Oral Valiltramiprosate on Plasma p-tau217 and p-Tau217/Aβ42 Ratio in APOE4/4 Homozygotes and their Correlations to Clincial and Imaging Outcomes: Results of Phase 3 APOLLOE4 Clinical Trial in Early AD (CTAD 2026) - No abstract available

Clinical • P3 data • Aβ42

Valiltramiprosate Improves Hippocampal Microstructure and Clinical Outcomes in APOE4/4: Phase 3 DTI and vMRI in Early AD (AAIC 2026) - No abstract available

Clinical • Clinical data • P3 data

Valiltramiprosate Reduced ARIA Rates In APOE4/4 With Early AD: Results Of Phase 3 APOLLOE4 Trial And CAA Implications (AAIC 2026) - No abstract available

P3 data

Oral Valiltramiprosate Shows Sustained CDR-SB Benefit Over 2.5 Years In APOE4/4 MCI Subjects: APOLLOE4 Phase 3 Long-term Extension Results (AAIC 2026) - No abstract available

Clinical • P3 data

Significant Positive Correlations Between Microstructure And Efficacy/Brain Atrophy Of Oral Valiltramiprosate In APOE4/4 MCI Subjects (AAIC 2026) - No abstract available

Clinical

Safety Of Oral ALZ-801 In APOE4/4 And APOE3/4 Subjects With Early AD In Long-term Extension Studies Up To 4 Years (AAIC 2026) - No abstract available

Clinical

Oral Valiltramiprosate Maintenance Therapy After Donanemab And Lecanemab Treatment: QSP Analysis Of Amyloid Aggregation By APOE Genotype (AAIC 2026) - No abstract available

Clinical • APOE

Valiltramiprosate In Biomarker-positive APOE4/4 MCI Subjects Shows Clinical Stability And Slows Atrophy Over 4-years (AAIC 2026) - No abstract available

Biomarker • Clinical

Valiltramiprosate Effects On Cerebellar Volume In APOE4/4 Early Alzheimer's Disease Subjects From Phase 3 APOLLOE4 Study (AAIC 2026) - No abstract available

Clinical • P3 data • Alzheimer's Disease • CNS Disorders

Valiltramiprosate On Plasma p-Tau217, p-Tau217/Ab42, vMRI And Clinical Correlations In Phase 3 APOE4/4 Early AD Subjects (AAIC 2026) - No abstract available

Clinical • P3 data

Evaluating emerging amyloid-β centric drugs for the treatment of Alzheimer's disease. (PubMed, Expert Opin Emerg Drugs) - "The recent approvals of lecanemab and donanemab offered the first convincing evidence that reducing Aβ burden can modestly slow cognitive decline in early AD. Beyond these first-generation monoclonal antibodies, the pipeline includes next-generation antibodies with enhanced brain penetration (trontinemab), therapies designed also for presymptomatic intervention (remternetug tested for secondary prevention), and novel approaches targeting galectin-3 to disrupt Aβ aggregation and neuroinflammation. Active immunotherapies like UB-311 and small molecules such as ALZ-801, avoiding amyloid-related imaging abnormalities (ARIA), broaden the therapeutic horizon with potentially safer and more accessible options, but with no proven efficacy...Regulators have begun to restrict approval to genetically defined subgroups according to apolipoprotein E genotype, underscoring the need for precision medicine. Therefore, while Aβ-centric therapies are incremental, they represent essential..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • APOE

APOLLOE4-LTE: Long-term Extension of Phase 3 Study of ALZ- 801 in APOE4/4 Early AD Subjects (clinicaltrials.gov) - P3 | N=163 | Terminated | Sponsor: Alzheon Inc. | Active, not recruiting ➔ Terminated; Sponsor business decision

Biomarker • Trial termination • Alzheimer's Disease • CNS Disorders

Tramiprosate, the Active Agent of ALZ-801, Modulates Amyloidogenic APP Processing and Tau Phosphorylation in a Cellular Model of Alzheimer's Disease. (PubMed, Drug Dev Res) - "Increased phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, without altering total GSK-3β levels, suggests that GSK-3β inhibition underlies the decrease in tau phosphorylation at these sites. As a result, tramiprosate's impact on both amyloidogenic APP processing and tau phosphorylation reveals its potential to modify AD."

Journal • Alzheimer's Disease • CNS Disorders • APP • Aβ42

APOLLOE4-LTE: Long-term Extension of Phase 3 Study of ALZ- 801 in APOE4/4 Early AD Subjects (clinicaltrials.gov) - P3 | N=163 | Active, not recruiting | Sponsor: Alzheon Inc. | Trial completion date: Jan 2027 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Jun 2026

Biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Effects of ALZ-801 on amyloid protein aggregation and cytotoxicity (JSNE 2026) - No abstract available

Alzheimer's Disease • CNS Disorders • Dementia

Safety and ARIA Analyses of Oral Anti-amyloid Oligomer Agent Valiltramiprosate in APOE4/4 Homozygotes with Early Alzheimer’s Disease (AD): Results of the Phase 3 78-week APOLLOE4 Trial (AAN 2026) - P3 | "ARIA-E rates were similar between treatment arms (~3%), ARIA-H was lower with valiltramiprosate treatment, and no ARIA events were symptomatic. Coupled with promising efficacy in MCI, valiltramiprosate provides a favorable benefit-risk profile for APOE4/4 AD patients with unmet need for safe and effective disease-modifying treatments."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders • Hematological Disorders

Clinical Effects of Oral Valiltramiprosate Treatment in APOE4 Carriers with Mild Cognitive Impairment (MCI): Results of the Phase 2 Study Long-term Extension over 3 Years (AAN 2026) - P3 | "These clinical benefits are supported by significant correlations to slowing of hippocampal atrophy. These long-term clinical benefits and favorable safety support oral valiltramiprosate as a promising potential treatment for APOE4 carriers with MCI."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders

Correlations between Clinical and Brain Volume Effects of Oral Valiltramiprosate in APOE4/4 Homozygotes with MCI: Pre-specified Analyses of the Phase-3 APOLLOE4 78-Week Trial in APOE4/4 Homozygotes with Early Alzheimer’s Disease (AD) (AAN 2026) - P3 | "Hippocampal and whole-brain volume effects showed significant subject-level correlations with cognitive and functional benefits over 78 weeks (correlations 0.45-0.49). These strong subject-level imaging-clinical correlations support the efficacy of valiltramiprosate in APOE4/4 MCI subjects."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders