- |||||||||| Aduhelm (aducanumab) / Neurimmune, Eisai, crenezumab (RG7412) / AC Immune
Journal: Directed evolution of drug-like A? conformation-specific antibodies. (Pubmed Central) - Oct 29, 2025
antibodies, including aducanumab and crenezumab. This antibody engineering platform can be readily applied to generate conformational antibodies against diverse types of peptide and protein aggregates linked to human diseases.
- |||||||||| JNJ-2056 / J&J, JACI-35.054 / AC Immune, J&J
P1/2 data, Journal, IO biomarker: Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study. (Pubmed Central) - Oct 10, 2025
P1/2
ACI-35.030 and JACI-35.054 were well tolerated. ACI-35.030 induced a more rapid and sustained antibody response selective to p-Tau species with evidence of altering AD-related plasma biomarkers and was selected for testing in the ongoing Phase 2b trial.
- |||||||||| JNJ-2056 / J&J
Trial completion date, IO biomarker: Re?ain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - Jun 27, 2025
P2, N=498, Recruiting,
Prioritizing mAbs with controlled amyloid clearance, C-terminal binding domains, and IgG1 frameworks may enhance therapeutic safety, advancing precision immunotherapy for Alzheimer's disease. Trial completion date: May 2033 --> Jul 2034
- |||||||||| semorinemab (RG6100) / AC Immune
Clinical, Journal: CSF proteomics of semorinemab Alzheimer's disease trials identifies cell-type specific signatures. (Pubmed Central) - May 28, 2025
P2
The elevation of proteins such as CHI3L1 and GPNMB with treatment suggested an activated glial state. This study demonstrates the utility of CSF clinical proteomics to assess the pharmacodynamic response of semorinemab and contributes to our understanding of how an anti-tau antibody influences disease-relevant pathophysiology in AD.
- |||||||||| JNJ-2056 / J&J
IMMUNIZATION WITH JNJ-64042056 GENERATES ANTIBODIES IN NON-HUMAN PRIMATES THAT INHIBIT TAU AGGREGATION IN A NEURONAL TAU SEEDING MODEL () - Mar 10, 2025 - Abstract #ADPD2025ADPD_1837;
This study demonstrates the utility of CSF clinical proteomics to assess the pharmacodynamic response of semorinemab and contributes to our understanding of how an anti-tau antibody influences disease-relevant pathophysiology in AD. JNJ-64042056, an active immunotherapy currently in clinical trials for the treatment of AD, induces the generation of polyclonal antibodies in NHP which displayed the functional capacity of inhibiting Tau aggregation in a rodent neuronal model.
- |||||||||| HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON (Hall E) - Mar 10, 2025 - Abstract #ADPD2025ADPD_729;
BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD.
- |||||||||| JNJ-2056 / J&J
ANTIBODIES GENERATED BY JNJ-64042056, AN ACTIVE ANTI-PTAU IMMUNOTHERAPY, IN CLINICAL TRIAL ACI-35-1802 CAN BLOCK TAU SEEDING IN NEURONS. (Hall E) - Mar 10, 2025 - Abstract #ADPD2025ADPD_726;
P2
Conclusions This work demonstrates that JNJ-64042056 induces an immune response in patients with AD that is capable of binding to AD-tau seeds and, therefore, has the potential to prevent tau aggregation induction and spreading in the human brain, which is the intended mode of action set for this anti-tau active immunotherapy. JNJ-64042056 is currently being tested in participants who have preclinical AD with confirmed tau pathology (ReTain Phase 2b trial, NCT06544616).
- |||||||||| semorinemab (RG6100) / AC Immune
Biomarker, Journal: Developing Topics. (Pubmed Central) - Jan 12, 2025
P2
We replicated prior speech biomarker findings in an independent, more severe AD population, suggesting that the speech characteristics within this score are robust and aligned with clinical progression across disease stages. Additional validation work is ongoing, including the development of comparative biomarkers leveraging the combined dataset.
- |||||||||| semorinemab (RG6100) / AC Immune
Biomarker, Journal: Biomarkers. (Pubmed Central) - Jan 12, 2025
Six CSF proteins highly correlated with tau PET were identified. Validation of these results by replicating the analysis on a secondary dataset with PET and CSF protein measurements may establish further confidence in these findings.
- |||||||||| ACI-24.060 / Takeda
Biomarker, Clinical, Journal: Biomarkers. (Pubmed Central) - Jan 12, 2025
Validation of these results by replicating the analysis on a secondary dataset with PET and CSF protein measurements may establish further confidence in these findings. Data from longitudinal biomarker studies are informing the design and conduct of clinical trials targeting AD in people with DS.
- |||||||||| Review, Journal: Developing Topics. (Pubmed Central) - Jan 12, 2025
The score range for CDR-SB is 0 to 18; the range for ADAS-Cog is 0 to 70/90. These mean differences across the many trials conducted cannot be considered to be either clinically or statistically significant.
- |||||||||| Leqembi (lecanemab-irmb) / Biogen, Eisai, ACI-24.060 / Takeda, Kisunla (donanemab-azbt) / Eli Lilly
Journal: Drug Development. (Pubmed Central) - Jan 12, 2025
Induced antibodies were in the range of levels of donanemab and lecanemab relevant for Abeta clearance in human AD patients. Therefore, ACI-24.060, with its dual target effect (pyroglutamate-Abeta and Abeta oligomers) and its FDA Fast Track designation, represents a potential breakthrough active immunotherapy for Alzheimer's disease.
- |||||||||| semorinemab (RG6100) / AC Immune
Journal: Drug Development. (Pubmed Central) - Jan 12, 2025
P2
Data from the two semorinemab trials suggest that there may be regional differences in the impact of study partner type on retention. Further studies are needed to assess the generalizability of these findings, with an emphasis on cohorts with more representative samples of non-spousal dyads.
- |||||||||| semorinemab (RG6100) / AC Immune
Journal: Drug Development. (Pubmed Central) - Jan 12, 2025
P2
The anchor- and distribution-based approaches suggest that clinically meaningful change on the ADCS-ADL may be greater than the 2 points that has previously been postulated (Dysken et al., 2014). Higher change thresholds may be required to reflect meaningful changes perceptible to caregivers.
- |||||||||| Review, Journal: An update on immune-based alpha-synuclein trials in Parkinson's disease. (Pubmed Central) - Dec 12, 2024
Despite some promising results, challenges such as variable efficacy and trial discontinuations persist. Future research must address these challenges to advance disease-modifying therapies for PD around this therapeutic target.
- |||||||||| semorinemab (RG6100) / AC Immune
PK/PD data, Journal: Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies. (Pubmed Central) - Oct 1, 2024
Our target-mediated drug disposition model adequately described the serum pharmacokinetics and the peripheral non-linear increase with dose of the total tau. The model confirmed that these dose-response relationships were consistent across populations of healthy volunteers and subjects with different severities of Alzheimer's disease.
- |||||||||| gosuranemab (BIIB092) / Biogen, bepranemab (UCB0107) / Roche, semorinemab (RG6100) / AC Immune
Synthetic receptors for programmable tau-responsive cellular therapies (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3367;
We envision tau receptors being used in a cell-based therapy, outfitting microglia and astrocytes with novel therapeutic behaviors. In neurons, tau receptors may serve as useful tools for reporting the extent of local tau pathology in real-time.
- |||||||||| ACI-24 / AC Immune
Journal: Prediction of the 3D conformation of a small peptide vaccine targeting A?42 oligomers. (Pubmed Central) - Jul 15, 2024
oligomers. This work provides a feasible implementation scheme of immunoinformatic and MD simulations for the development of AD small peptide vaccines, validating the power of the scheme as a parallel tool to the experimental approaches and injecting molecular-level information into the understanding and design of anti-AD vaccines.
- |||||||||| Review, Journal: Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders. (Pubmed Central) - Jun 27, 2024
The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively.
- |||||||||| semorinemab (RG6100) / AC Immune
Identification of CSF proteins in Alzheimer (Exhibit (Pennsylvania Convention Center); In-Person) - Jun 19, 2024 - Abstract #AAIC2024AAIC_2843;
Method : AD CSF samples were from participants enrolled in Tauriel or Lauriet, two semorinemab PhII trials...Conclusion : Six CSF proteins highly correlated with tau PET were identified. Validation of these results by replicating the analysis on a secondary dataset with PET and CSF protein measurements may establish further confidence in these findings.
- |||||||||| Review, Journal: A Review of Recent Advances in the Management of Alzheimer's Disease. (Pubmed Central) - May 17, 2024
Additional anti-inflammatory agents being currently tested in phase-2 clinical trials, such as atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), and benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, drugs targeting Alzheimer's-associated symptoms, such as brexpiprazole (serotonin dopamine activity modulator) and suvorexant (orexin receptor antagonist), respectively, used for agitation and insomnia in AD patients, are reviewed.
- |||||||||| Review, Journal: Alzheimer's disease and clinical trials. (Pubmed Central) - Apr 1, 2024
A meticulous prior assessment of the outcome of clinical studies may stop risky clinical trials at their inceptions. This may save time, money, and resources.
- |||||||||| semorinemab (RG6100) / AC Immune, solanezumab (LY2062430) / Eli Lilly
Fall-Related Risks with Pharmacological Interventions in Mild-to-Moderate Alzheimer () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_349;
The results should be interpreted cautiously as the risks and benefits alter with disease progression and change in symptoms. Further long-term studies directly comparing the effect of these interventions on risk of falls and confirmation of their sustainability is warranted.
- |||||||||| crenezumab (RG7412) / Roche
Journal: Re-Engineering Therapeutic Anti-A? Monoclonal Antibody to Target Amyloid Light Chain. (Pubmed Central) - Feb 14, 2024
antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies...It is capable of reversing A?42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.
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