alhydrogel injectable (AD04) / ADvantage Therap - LARVOL DELTA

Developing Topics. (PubMed, Alzheimers Dement) - "Based on these preclinical results we conclude that AD04 administration induces microglia to phagocytose brain debris, such as apoptotic neurons, synapses and degraded myelin in the aged brain, and in the AD brain also Abeta, extracellular tau tangles and oxidized lipids. By changing the microglial phenotype, AD04, indirectly reduces the neuroinflammation induced by Abeta, tau and neuronal debris, leading to an anti-inflammatory milieu in the brain which protects and rescues the hippocampus from neurodegeneration."

IO biomarker • Journal • Allergy • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Metabolic Disorders

ADvantage Therapeutics Announces Breakthrough Findings in Alzheimer's Disease Treatment: AD04TM shows immediate symptomatic and disease-modifying properties (GlobeNewswire) - "Treatment with AD04 significantly restored the expression of proteins involved in lipid metabolism in aged mice, aligning their levels with those of young mice. This restoration is believed to contribute to the therapeutic effects observed....Key proteins in lipid metabolism, such as ACSL1, were found to be upregulated after AD04 treatment. This suggests that the therapeutic benefits of AD04 are closely tied to the modulation of hippocampal lipid metabolism."

Preclinical • Alzheimer's Disease

AD04 – modifying Alzheimer’s Disease by modulation of neuroinflammation (AAIC 2024) - "Based on these preclinical results we conclude that AD04 administration induces microglia to phagocytose brain debris, such as apoptotic neurons, synapses and degraded myelin in the aged brain, and in the AD brain also Abeta, extracellular tau tangles and oxidized lipids. By changing the microglial phenotype, AD04, indirectly reduces the neuroinflammation induced by Abeta, tau and neuronal debris, leading to an anti-inflammatory milieu in the brain which protects and rescues the hippocampus from neurodegeneration."

IO biomarker • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Metabolic Disorders

"Time Saved" Calculations to Improve Decision-Making in Progressive Disease Studies. (PubMed, J Prev Alzheimers Dis) - "The relevance of 11 months saved is more universally understood than a mean difference of 3.8 points in the composite outcome. These results suggest that a combination of a composite approach and a time savings interpretation offers a powerful approach for detecting and interpreting disease modifying effects."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders

DESIGN OF A RANDOMIZED PHASE 2B, PLACEBO-CONTROLLED TRIAL ASSESSING SAFETY AND EFFICACY OF AD04 IN EARLY ALZHEIMER'S DISEASE ("ADVANCE") (ADPD 2024) - "The ADVANCE RCT is evaluating a novel immune-stimulating intervention for patients with early AD, based on evidence from AFF006 (phase 2). The study has a high estimated probability of success."

Clinical • P2b data • Alzheimer's Disease • CNS Disorders

ADvantage Therapeutics Has Commenced Enrollment for Its Phase 2b Clinical Trial of AD04 for Treatment of Alzheimer’s Disease (GlobeNewswire) - "ADvantage Therapeutics, Inc...today announced the first patient enrolled in the Company’s European Phase 2b clinical trial on its lead candidate, AD04 for the treatment of mild Alzheimer’s disease (AD)....The primary endpoint of the 12-month study is to be a composite score integrating ADAScog, ADCS-ADL and CDR-sb (at 6 months). Other measured outcomes include hippocampal volume, CDR-sb, the Neuropsychiatric Inventory (NPI), the Alzheimer’s disease Assessment scale – cognition 13-item scale (ADAScog13), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living Standards (ADCS-ADL), and the patient Quality-of-Life-Alzheimer’s disease."

Enrollment open • Alzheimer's Disease • CNS Disorders

Time saved in disease progression for treatments in AD (including 3 monoclonal antibodies and 2 other promising treatments) (AAIC 2023) - " Results for five studies of interest (three monoclonal antibodies and two other treatments) Aducanumab, Donanemab, Lecanemab, AD04, and Souvenaid show time savings range from 2 months per year to 7 months per year. Measuring time savings in a degenerative disease reflects the true goal of disease modifying treatments which is to slow down a progressive disease which will result in slowing of progression on all aspects or symptoms of disease. Progressive diseases would cease to be diseases at all if there was no progression of symptoms. Focusing on the clinical meaningfulness of each separate point on each outcome distracts us from this overall goal."

Alzheimer's Disease • CNS Disorders

ADvantage Therapeutics Secures Approvals for Clinical Trial of AD04 in Alzheimer’s Disease Treatment in Poland, Bulgaria, and Slovakia (GlobeNewswire) - "ADvantage Therapeutics, Inc...announced that regulatory authorities in Poland, Bulgaria, and Slovakia have approved its Clinical Trial Application (CTA) to conduct a clinical trial on its lead candidate, AD04™ for the treatment of mild Alzheimer’s disease (AD) in each respective country. The Phase 2b study authorized in these countries will be a randomized, double-blind, placebo-controlled trial aimed at confirming proof-of-concept and establishing the safety and efficacy of AD04™ in patients with mild AD."

New P2b trial • Alzheimer's Disease • CNS Disorders

MHRA Grants ADvantage Therapeutics Innovative Licensing and Access Pathway (ILAP) Designation for Novel Lead Product AD04 for Phase 2b Trial in Alzheimer’s Disease (GlobeNewswire) - "ADvantage Therapeutics, Inc...announced that the Medicines and Healthcare products Regulatory Agency (MHRA), the United Kingdom National Competent Authority, has granted the Company’s lead compound AD04™ an Innovation Passport for the treatment of AD under the Innovative Licensing and Access Pathway (ILAP)....The Phase 2b trial for AD04™ in the ILAP application will be a randomized, placebo-controlled, double-blind study to confirm proof of concept and establish the safety and efficacy of AD04™ in mild AD patients."

European regulatory • Alzheimer's Disease • CNS Disorders

ADvantage Therapeutics Developing Therapies to Treat Neurodegenerative Conditions with Focus on Alzheimer’s Disease (GlobeNewswire) - “ADvantage Therapeutics, Inc…announces it is working on the development of its lead candidate, the AD04™ compound for the treatment of early Alzheimer’s disease (AD)….To date, preclinical studies have shown that AD04™ decreased the number of inflammatory microglial cells in the hippocampus of mouse models....The Company has applied for clinical trial authorization (CTA) in six European countries to conduct a Phase 2b confirmatory trial designed to verify and enhance the current understanding of the product in the context of treating early Alzheimer’s disease. The Phase 2b study will be a randomized, placebo-controlled, double-blind study designed to confirm proof-of-concept and establish safety and efficacy of AD04™ (injectable alhydrogel) in early AD patients. The 12-month study will measure hippocampal volume as a primary objective/biomarker endpoint.”

Clinical protocol • New P2b trial • Preclinical • Alzheimer's Disease • CNS Disorders

Evaluation of differences in HLA-DR4 gene and its subtypes prevalence among healthy people and RA patients in Isfahan province population. (PubMed) - Adv Biomed Res - "The observed differences between prevalence of HLA-DR4 gene between the case and control group were not statistically significant (P = 0.45; OR = 1.256; 95% CI = 0.69-2.27), but a relation was between HLA-DR4 0404 subtypes and RA (P = 0.02; OR = 0.44; 95% CI = 0.196-0.992)."

Journal • Biosimilar • Rheumatoid Arthritis