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

BIOMARKER-POSITIVE APOE4 CARRIERS WITH MCI SHOW DISEASE STABILITY OVER 4-YEARS OF VALILTRAMIPROSATE/ALZ-801 TREATMENT: MMSE RESPONDER ANALYSIS FROM THE ALZ-801 PHASE 2 LONG-TERM EXTENSION STUDY (ADPD 2026) - "Valiltramiprosate treatment of APOE4-carrier MCI subjects with confirmed AD pathology showed high proportion of subjects with stable disease stage over 2-4 years (MMSE drop ≤4). Cognitive stability in APOE4/4 MCI group remained high with 86% and 73% at 2 and 4 years. Consistent with the Phase 3 results (Abushakra, ADPD2026), valiltramiprosate shows promising benefit-risk profile in homozygotes with MCI."

Biomarker • P2 data • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease

SAFETY AND ARIA ANALYSES OF THE ORAL ANTI-AMYLOID OLIGOMER AGENT VALILTRAMIPROSATE IN APOE4/4 HOMOZYGOTES WITH EARLY AD: RESULTS OF THE 78-WEEK PHASE 3 APOLLOE4 TRIAL (ADPD 2026) - "Valiltramiprosate was well tolerated with favorable safety over 78 weeks consistent with prior studies in >3000 AD patients. ARIA-E rates were similar between valiltramiprosate and placebo arms (~3%), ARIA-H was lower than placebo, and no ARIA events were symptomatic. Coupled with promising efficacy in MCI subjects, valiltramiprosate provides a favorable benefit-risk profile for high-risk APOE4/4 patients with unmet need for safe and effective disease-modifying treatments."

Clinical • P3 data • Hematological Disorders

VALILTRAMIPROSATE EFFECTS IN THE PRE-SPECIFIED MCI GROUP SHOW SIGNIFICANT CORRELATIONS BETWEEN CLINICAL AND BRAIN VOLUME BENEFITS: PHASE-3 APOLLOE4 RESULTS IN EARLY AD APOE4/4 HOMOZYGOTES (ADPD 2026) - "In APOLLOE4 pre-specified MCI group, valiltramiprosate showed nominally significant cognitive and functional benefits with significant atrophy slowing in all brain compartments (HV 26%, WBV 22%). Hippocampal and whole-brain volume effects showed significant subject-level correlations with cognitive and functional benefits over 78 weeks (correlations 0.45-0.49). In the MCI population with adequate neuronal reserve, valiltramiprosate effects on neurodegeneration translate to meaningful clinical efficacy with favorable safety in APOE4/4 homozygotes."

Clinical • P3 data • CNS Disorders

POSITIVE EFFECTS OF ORAL VALILTRAMIPROSATE ON GREY AND WHITE MATTER MICROSTRUCTURAL INTEGRITY BY DTI IN APOE4/4 HOMOZYGOTES WITH EARLY AD: APOLLOE4 78-WEEK PHASE 3 RESULTS (ADPD 2026) - "In the pre-specified MCI group, valiltramiprosate reduced mean water diffusivity in grey/white matter regions, most prominent in areas affected early in MCI (cingulate cortex/ fornix/corpus callosum). These effects correlated significantly with its positive clinical/brain-volume benefits, suggesting preservation of the brain's microstructural integrity. Together, these imaging findings suggest slowing of neurodegeneration, and support valiltramiprosate's efficacy in APOE4/4 MCI patients."

P3 data • CNS Disorders

QUANTITATIVE SYSTEMS PHARMACOLOGY ANALYSES OF BETA-AMYLOID AGGREGATION DYNAMICS: ADDITIVE/SYNERGISTIC EFFECTS OF VALILTRAMIPROSATE USED IN COMBINATION WITH LEQEMBI AND KISUNLA (ADPD 2026) - "Valiltramiprosate acts upstream in the beta-amyloid cascade to prevent the formation of toxic soluble oligomers. Valiltramiprosate when used in combination with Leqembi or Kisunla offers potential additive and synergistic benefits that translate into reduction of oligomer, protofibril and/or plaque burden. The combination effects were dependent on APOE4 genotype and disease stage."

Combination therapy • Alzheimer's Disease • CNS Disorders • APOE

VALILTRAMIPROSATE REVERSES NEURODENEGERATION AND IMPROVES CLINICAL OUTCOMES IN SUBGROUP OF EARLY SYMPTOMATIC AD IN HOMOZYGOTES: RESULTS FROM 78 WEEK PHASE 3 APOLLOE4 TRIAL (ADPD 2026) - "Valiltramiprosate reversed hippocampal atrophy and stabilized cognition/function over 78 weeks in a subgroup of early symptomatic AD subjects. The increased HV in this subgroup suggests a beneficial effect of valiltramiprosate on neurogenesis/neuroplasticity and supports its potential as a preventive treatment for APOE4/4 presymptomatic AD patients."

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

CLINICAL STABILIZATION IN MCI APOE4 CARRIERS OVER 3 YEARS CORRELATES WITH IMPROVED HIPPOCAMPAL VOLUME IN VALILTRAMIPROSATE PHASE 2 LTE STUDY (ADPD 2026) - "Valiltramiprosate showed cognitive stabilization over 3 years in APOE4 carriers with MCI similar to the prespecified MCI benefit in APOLLOE4 Phase 3 trial in APOE4 homozygotes. The clinical effects are corroborated by positive correlation between cognitive benefit and HV effects over 3 years. These benefits together with favorable safety, support evaluation of oral valiltramiprosate as a potential therapy for APOE4 carriers with early symptomatic AD."

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

CLINICAL EFFICACY AND IMAGING RESULTS OF ORAL VALILTRAMIPROSATE IN APOE4/4 HOMOZYGOTES WITH EARLY AD: PHASE 3 TOPLINE RESULTS FROM THE 78-WEEK APOLLOE4 TRIAL (ADPD 2026) - "Overall Early AD population did not show significant effects on clinical outcomes but showed 18% and 16% slowing of hippocampal and whole brain atrophy, respectively. Pre-specified MCI showed significant benefits (nominal) on ADAS-Cog13 (52%), DAD (96%), positive CDR-SB trend, and significant slowing of atrophy across all brain regions (22%-35%), with no increased ARIA. Valiltramiprosate's favorable benefit-risk profile supports its potential as a treatment for high-risk APOE4/4 homozygotes with MCI."

Clinical • P3 data • P3 data: top line

Alzheon…announced it will present new efficacy, imaging, safety, biomarker, and quantitative systems pharmacology findings for its lead investigational therapy, valiltramiprosate/ALZ-801 during the 2026 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD)… (Businesswire) - "Two oral presentations and six posters highlight consistent effects of oral valiltramiprosate on brain volume, microstructural integrity, neurodegeneration, systems modeling, and long-term clinical stability....New results to be presented at AD/PD include safety and ARIA analyses from the APOLLOE4 Phase 3 placebo-controlled trial, quantitative systems pharmacology (QSP) analyses of amyloid aggregation dynamics, diffusion MRI findings showing preserved microstructural integrity, and clinical-imaging correlations in the pre-specified Mild Cognitive Impairment (MCI) subgroup of the Phase 3 study."

Biomarker • Clinical data • Alzheimer's Disease

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 | "In this placebo-controlled trial, valiltramiprosate was well tolerated with favorable safety over 78-weeks. Gastrointestinal AEs were typically mild/moderate and transient, weight loss either resolved or stabilized. ARIA-E rates were similar between treatment arms (~3%), ARIA-H was lower with valiltramiprosate treatment, and no ARIA events were symptomatic."

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 | "Valiltramiprosate effects in MCI APOE4 carriers, including APOE4/4 homozygotes, over 3 years showed similar cognitive benefits to the MCI APOE4/4 group from the Phase 3 study. 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 | "In the Phase 3 pre-specified MCI group, valiltramiprosate showed nominally significant cognitive and functional benefits with statistically significant atrophy slowing in all brain compartments (HV 26%, WBV 22%). 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

Biomarker-positive APOE4 Carriers with MCI Show Cognitive Stability over 4 Years of Oral Valiltramiprosate/ALZ-801 Treatment: MMSE Responder Analysis from the ALZ-801 Phase 2 Long-term Extension Study (AAN 2026) - "Amyloid positive, APOE4 carriers with Early AD treated with valiltramiprosate show high rate of stabilized MMSE scores (responders) over 4 years, particularly in subject with MCI (58% at 4 years). Long-term safety over 4 years of treatment was favorable with no ARIA-E or symptomatic ARIA-H. Analyses of Additional clinical, volumetric and biomarker analyses are in progress."

Biomarker • P2 data • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease

Effects of Oral Valiltramiprosate on Clinical Efficacy, Safety, and Brain Volume Outcomes in APOE4/4 Homozygotes with Early Alzheimer's Disease (AD): Topline Results of the 78-week Phase 3 APOLLOE4 Trial (AAN 2026) - P3 | "The overall population did not achieve significance on primary/secondary clinical outcomes, but showed significant slowing of hippocampal atrophy on valiltramiprosate (18% p=0.017). The pre-specified MCI group showed nominally significant positive effects on cognitive and functional outcomes, with 52% less cognitive decline, functional stabilization, significant slowing of hippocampal (26%) and whole brain atrophy (22%) over 78 weeks. Overall safety was favorable with no increased ARIA-E or ARIA-H."

Clinical • P3 data • P3 data: top line • Alzheimer's Disease • CNS Disorders

Reassessing Amyloid Modulation: Clinical Efficacy and Safety of Valiltramiprosate in Alzheimer's Disease (AAN 2026) - "Studies for ALZ-801 in early AD population showed no notable clinical efficacy in the overall study population at 78 weeks. Nevertheless, the MCI subgroup reported significant reduction in brain atrophy progression and functional decline. No increase in ARIA or serious adverse events were evident, highlighting the safety and tolerability of the drug."

Clinical • Alzheimer's Disease • Anorexia • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders • APOE

Behavioral Neurology and Neuropsychiatry Section Poster Tour (AAN 2026) - "If you are interested in attending, visit the poster hall and look for the tour guide holding the yellow Poster Tour sign. Featured abstracts:Anti-tau Therapies in Alzheimer's Disease: Systematic Review and Meta-analysis of Advanced-phase Randomized Clinical TrialsTop-line Results from evoke and evoke+: Two Phase 3, Randomized, Placebo-controlled Trials of Semaglutide in Participants with Early-stage Symptomatic Alzheimer's DiseaseRepurposed Drugs for Alzheimer's Disease: Integrating Mechanistic Efficacy and Global Feasibility Through a Translational Decision MatrixNovel Mechanistic Roles for TMEM106B in Regulating Lysosomal Inter-organelle Contact Sites and Misregulation in Frontotemporal DementiaDifferential Response to Transcranial Direct Current Stimulation Across Primary Progressive Aphasia Subtypes: A Case Study AnalysisDose-dependent Efficacy and Safety of Brexpiprazole in Agitation Associated with Dementia in Alzheimer's Disease: A Systematic..."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Psychiatry

Alzheon Reports Plasma Biomarker Results from Phase 3 and 2 Studies of Valiltramiprosate/ALZ-801, Validating Its First-in-Class Mechanism of Action and Underscoring Benefits in Cognition, Function, and Brain Volume Protection in Alzheimer’s Patients (Businesswire) - "Across both studies, the majority of participants satisfied criteria for AD positivity in accordance with the recently FDA-approved plasma p-tau217/Aβ1-42 ratio. In the Phase 3 APOLLOE4 trial involving APOE4/4 homozygotes, 94% of enrolled subjects were confirmed as AD positive, and in the Phase 2 trial targeting APOE4 carriers that utilized CSF biomarkers as inclusion criteria, 97% of homozygote and 96% of heterozygote patients met the AD positivity threshold....'In 2026, we will move forward with our plans for the next Phase 3 study based on analyses from the APOLLOE4 Phase 3 trial and its long-term extension'."

Biomarker • Clinical data • New P3 trial • Alzheimer's Disease

Therapeutic Potential of Oral ALZ-801 in Patients with Alzheimer's Disease. (PubMed, Intern Med) - "In the APOLLOE4 Phase 3 study of ALZ-801 in apolipoprotein E ε4 homozygous patients with early AD, the primary endpoint was not achieved; however, the mild cognitive impairment subgroup demonstrated nominal efficacy. ALZ-801 has not been associated with amyloid-related imaging abnormalities, a major safety concern of anti-Aβ antibodies, and may represent a safe oral alternative to anti-Aβ antibody therapies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE

Drug Development. (PubMed, Alzheimers Dement) - P1 | "AS-S603 is a first-in-class oral treatment for AD, uniquely targeting both Aβ and tau aggregates. It provides significant cognitive benefits in preclinical studies, suggesting its potential to alter disease progression. Clinical studies will validate its safety and efficacy, positioning AS-S603 as a transformative treatment for AD."

Journal • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "These strong correlations between structural preservation and clinical benefits of valiltramiprosate at the MCI stage support its efficacy and are consistent with its proposed mechanism of inhibiting amyloid oligomer formation, thereby potentially protecting neurons from synaptic dysfunction and neurodegeneration. Given the accelerated neurodegeneration in APOE4/4 patients, these findings suggest that intervention at the early stages of AD when neuronal reserve is higher, may be critical for valiltramiprosate to exert meaningful clinical effects alongside preservation of brain structure and volume."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Developing Topics. (PubMed, Alzheimers Dement) - "QSP analysis supports the hypothesis that acceleration of Aβ aggregation is the initial step in Early AD triggering an increase in toxic oligomers that drives AD neurodegeneration, measured by hippocampal atrophy, followed by subsequent rapid cognitive decline. Valiltramiprosate intervention in Early AD produces an exposure, age and stage of disease-dependent reduction in hippocampal atrophy in all APOE genotypes, with the magnitude of benefit greatest at early symptomatic disease stage. The neuroprotective effect is driven by an exposure-related reduction of Aβ oligomers and protofibrils that blunts the pathological amyloid cascade in AD."

Journal • CNS Disorders • Developmental Disorders • APOE

Developing Topics. (PubMed, Alzheimers Dement) - "Valiltramiprosate demonstrates potential for preventing hippocampal atrophy and stabilization of cognitive and functional decline in earliest symptomatic APOE4/4 AD. The results support a potential disease stabilization benefit of oral valiltramiprosate as a prevention therapy in presymptomatic AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Consistent with valiltramiprosate's effects on brain volumes, its effects on microstructural integrity were most prominent in the MCI subgroup that showed lower diffusivity in the cingulate cortex and major hippocampal outflow tracts. This microstructural preservation correlated significantly with preservation of HV/CT and with clinical benefits. These findings support valiltramiprosate's proposed mechanism: inhibiting oligomer formation may directly protect synapses/axons from damage, thus slowing neurodegeneration at a microstructural level and contributing to macrostructural preservation of brain volumes and clinical benefit."

Journal • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "In the overall population, ADAS-Cog13 did not achieve significance, but the hippocampus showed significant 18% slowing of atrophy. The pre-specified Mild group showed trends to HV atrophy slowing that did not translate to clinical benefits. The pre-specified MCI group showed significant 28% HV atrophy slowing with meaningful cognitive and functional benefits and positive trends on several secondary clinical outcomes. Overall safety was favorable with no increased ARIA. In the high-risk APOE4/4 population, this positive benefit-risk profile supports valiltramiprosate's potential as an oral disease-modifying treatment for APOE4/4 homozygotes with MCI."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Hematological Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "The results suggest that the primary molecular MOA driver of valiltramiprosate to reduce AD neurodegenerative pathology is mediated by its anti-aggregation action, which in turn prevents formation of soluble neurotoxic oligomers and protofibrils without directly reducing amyloid plaques load. The APOE4 corrector MOA of valiltramiprosate may partially contribute to its clinical efficacy in APOE4/4 and APOE4/3 AD patients by switching the phenotype to APOE3/3 phenotype."

Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • APOE