emrusolmin (TEV- '286) / MODAG, Teva - LARVOL DELTA

Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size. (PubMed, bioRxiv) - "Using two different anti-alpha-synuclein antibodies, our data suggests that [AgI(μ-L)] 3 decreases a C-terminal truncated protein that is approximately 12.4 kDa, as well as increases the size and alters the shape of PFF-induced aggregates. This indicates that [AgI(μ-L)] 3 impacts aggregation in a manner different from HL and may serve as a novel tool for studying C-terminal truncation related aggregation chemistry."

Journal • CNS Disorders

Anle138b mitigates post-hypoxic cognitive impairment, α-Synuclein aggregation and UPR activation in Drosophila melanogaster. (PubMed, Acta Neuropathol Commun) - "Anle138b significantly reduced α-Syn aggregation, repressing post-hypoxic PERK activation and improving survival and decision-making. Our findings demonstrate the effectiveness of anle138b in mitigating hypoxia-induced α-Syn aggregation and cognitive impairment, paving the way for future studies on its potential as a therapeutic strategy for PSCI."

Journal • CNS Disorders • Cognitive Disorders

Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease (Neuroscience 2025) - "Administration of anle138b in a second HD mouse model, the knock-in zQ175DN model, confirmed the small molecule's ability to decrease mutant HTT aggregate load and rescue neurochemical changes. Altogether these results suggest that anle138b is an effective approach in the treatment of HD."

Preclinical • CNS Disorders • Movement Disorders • CLSPN,

An Extension Trial to Test if TEV-56286 is Effective in Relieving Multiple System Atrophy (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Multiple System Atrophy

Anle138b binds predominantly to the central cavity in lipidic Aβ₄₀ fibrils and modulates fibril formation. (PubMed, Nat Commun) - "In addition, anle138b reduces fibril formation in the presence of lipids by approximately 75%. This may suggest a mechanistic connection to its previously reported activity in animal models of Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders

An Extension Trial to Test if TEV-56286 is Effective in Relieving Multiple System Atrophy (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC

New P2 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy

Teva’s Emrusolmin Granted U.S. FDA Fast Track Designation for Treatment of Multiple System Atrophy (GlobeNewswire)

Fast track • Multiple System Atrophy

A human striatal-midbrain assembloid model of alpha-synuclein propagation. (PubMed, Brain) - "Treatment with protein aggregation inhibitor (Anle138b) and autophagy inducer (Rapamycin) reduced α-syn aggregation, indicating potential of hSMAs for drug testing. This study established hSMAs as a novel platform for modeling PD, demonstrating α-syn propagation and associated neural pathologies. These assembloids offer significant potential for developing therapeutic strategies and understanding the mechanisms of PD progression."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • SNCA

A Study to Assess New Formulations of TEV-56286 (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | Recruiting ➔ Completed

Trial completion

Teva Reaffirms “Pivot to Growth” Strategy Progress with Launch of Acceleration Phase at 2025 Innovation and Strategy Day (Teva Press Release) - "AUSTEDO: Expected to exceed $2.5 billion in sales by 2027 and exceed $3 billion by 2030. AJOVY: A globally established brand with presence across 43 countries and expected launches in 3 additional countries this year....duvakitug (anti-TL1A): A potentially best-in-class treatment for inflammatory bowel disease, with potential expansion into additional indications with peak sales potential of up to $2-$5 billion. DARI: A dual-action rescue inhaler for asthma, that could address a significant unmet need as a first ICS/SABA combination for both adult and pediatric patient populations, with peak sales potential of ~$1 billion....emrusolmin: A potential first-in-class treatment for Multiple System Atrophy (MSA), a rare and fatal neurodegenerative disease that currently has no approved treatments, with peak sales potential of more than $2 billion. TEV-‘408...with peak sales potential of more than $1 billion."

Launch • Sales projection • Asthma • Crohn's disease • Huntington's Disease • Inflammatory Bowel Disease • Migraine • Multiple System Atrophy

A Study to Assess New Formulations of TEV-56286 (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC

New P1 trial

OPTIMIZING SPECIFICITY OF PET TRACERS FOR PROTEIN AGGREGATES: A MULTILEVEL APPROACH FROM IN VITRO SCREENING TO IN VIVO VALIDATION (ADPD 2025) - "This study presents a multi -tiered compound screening workflow, de signed to improve the diagnostic precision of novel PET tracers and validate target engagement for clinical drug candidates, such as emrusolmin... This preclinical tracer development workflow allowed us to confirm the target engagement of the drug candidate in clinical trials, highlighting its potential for diagnosing synucleinopathies and evaluating alpha -synu clein-targeted therapies using PET. This approach will ultimately advance the precision and effectiveness of NDD diagnostics and treatments."

Preclinical • CNS Disorders

EMRUSOLMIN A NOVEL Α-SYNUCLEIN TARGETING DRUG, IS EFFICACIOUS IN IN VITRO MODELS OF MULTIPLE SYSTEMS ATROPHY (ADPD 2025) - "These results demonstrate that emrusolmin inhibits α-syn aggregation in MSA in vitro models and that it does so in clinically relevant concentrations. Thus, these findings provide a foundation for further testing of emrusolmin's poten tial as a disease modifying agent in MSA patients."

Preclinical • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Solid Tumor

UPDATE ON TOPAS-MSA: AN ON-GOING PHASE 2 STUDY FOLLOWED BY AN OPEN-LABEL-EXTENSION STUDY OF EMRUSOLMIN IN MULTIPLE SYSTEM ATROPHY (ADPD 2025) - "Currently there are no therapies to slow or stop the rapid progression of neurodegeneration and associated disability. TOPAS-MSA will provide data on the treatment potential of emrusolmin for MSA with the OLE offering further long-term data."

Clinical • P2 data • CNS Disorders • Movement Disorders • Multiple System Atrophy

Slightly viscous oxidized alginate dispersions as vehicles for intranasal administration of the α-synuclein aggregation inhibitor Anle 138b in free form or encapsulated in solid lipid nanoparticles. (PubMed, Int J Pharm) - "Drug release studies employing SVDs and SNF/mucin mixture as release medium showed quantitative release of the inhibitor within 48 h. We conclude that Anle 138b SLN Alg OX/HPMC SVD constitutes a promising formulation due to its capability to provide the inhibitor in quantitative and sustained way, being not cytotoxic towards human RPMI 2650 cells and neuronal SH-SY5Y cells."

Journal

Mass Balance Clinical Trial With TEV-56286 (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting ➔ Completed

Trial completion

Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders. (PubMed, Int J Mol Sci) - "The most recent research focuses on finding potential applications targeting the pathological forms of proteins responsible for neurodegeneration. This review highlights the mechanisms relevant to protein-dependent neurodegeneration based on the most common disorders and describes current therapeutic approaches targeting protein misfolding and aggregation."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Lewy Body Disease • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Progressive Supranuclear Palsy • Solid Tumor

Mass Balance Clinical Trial With TEV-56286 (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Mass Balance Clinical Trial With TEV-56286 (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

New P1 trial

TOPAS-MSA: Targeting Oligomer Pathology of Alpha-Synuclein – A Study Evaluating the Safety and Efficacy of Emrusolmin in Patients with Multiple System Atrophy (MDS Congress 2024) - P1 | "There is a significant unmet medical need for MSA treatment as there are no therapies to address the underlying pathology of neurodegeneration. Thus, TOPAS-MSA will test emrusolmin as treatment for MSA. This abstract was previously presented as an oral presentation at AD/PD 24 on 8th March 2024."

Clinical • CNS Disorders • Multiple System Atrophy

TOPAS-MSA: A Study to Test if TEV-56286 is Effective in Relieving Multiple System Atrophy Safety and Efficacy Study (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

New P2 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy

Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins. (PubMed, Melanoma Res) - "We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized α-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses."

Journal • Metastases • CNS Disorders • Genetic Disorders • Melanoma • Movement Disorders • Oncology • Parkinson's Disease • Skin Cancer • Solid Tumor

Development of Positron Emission Tomography Agent for Alpha-Synuclein Imaging (SNMMI 2024) - "Our group identified several alpha-synuclein ligands with a better ADME profile than anle138b by in silico approach... A series of novel ligands based on the structure-activity relationship of carbazole, imidazolopyridine and imidazolopyrimidine were designed, and in silico docking studies were performed to obtain binding affinity of novel alpha-synuclein ligands. Based on ADME and in vitro assays, the lead ligand [11C]ASRN37 was radiolabeled and exhbited higher BBB penetration in mice."

Alzheimer's Disease • Anesthesia • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

Molecular docking analysis of α-Synuclein aggregation with Anle138b. (PubMed, Bioinformation) - "Protein-protein docking showed that Anle138b interferes with α-synuclein decamer formation. These results highlight the oligomer-directed inhibitory mechanism of Anle138b, without hindering the monomeric forms and provide molecular insights to advance its therapeutic development for Parkinson's and related synucleinopathies."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Anti-prion drugs do not improve survival in novel knock-in models of inherited prion disease. (PubMed, PLoS Pathog) - "None of the regimens tested (Anle138b, IND24, Anle138b + IND24, cellulose ether, and PSCMA) significantly extended disease-free survival or prevented mutant PrPSc accumulation in either knock-in mouse model, despite their ability to induce strain adaptation of mutant prions. Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions, as well as anti-prion strategies that are not strain-dependent."

Journal • CNS Disorders • Insomnia • Sleep Disorder