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

From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease. (PubMed, Metab Brain Dis) - "These include translation and misfolding inhibitors, aggregation modulators such as minzasolmin (UCB0599), epigallocatechin gallate and anle138b, as well as compounds that enhance α-Syn degradation through autophagy-lysosomal and ubiquitin-proteasome pathways. Beyond its pathogenic role, α-Syn contributes to synaptic vesicle trafficking, neurotransmitter release, and neuronal maturation, and disruption of these functions may increase vulnerability to later neurodegeneration. In conclusion, small-molecule-based therapies represent a promising multi-targeted strategy for PD; however, key translational challenges and unresolved questions remain, including optimisation of pharmacokinetics, target specificity, and blood-brain barrier (BBB) penetration and validation in clinical settings."

Journal • Review • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation

A Trial to Assess TEV-56286 at Different Doses in Healthy Participants (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases. (PubMed, Inflammopharmacology) - "Promising candidates such as anle138b and methylene blue display efficacy in preclinical models...This article examines the dual role of tau in physiology and pathology, highlighting its effects at both the cellular and subcellular levels. These findings underscore the critical importance of the tau protein in preventing NDs and suggest that a deeper understanding of its functions could improve treatment strategies for tau-related disorders."

Journal • Review • Alzheimer's Disease • CNS Disorders

A Trial to Assess TEV-56286 at Different Doses in Healthy Participants (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC

New P1 trial

Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease. (PubMed, EMBO Mol Med) - "Moreover, anle138b markedly decreased mHTT aggregation in human neural precursor cells differentiated from HD patient-derived induced pluripotent stem cells (iPSCs). Altogether these results illustrate the potential of anle138b as a disease-modifying treatment for HD."

Journal • Preclinical • CNS Disorders • Huntington's Disease • Inflammation • Movement Disorders

The PET tracer [11C]MODAG-005 targets alpha-synuclein aggregates in the brain. (PubMed, Sci Transl Med) - "To validate the potential of [11C]MODAG-005 for therapeutic development, we showed target engagement of the drug candidate anle138b in the brain tissues from α-synuclein (A30P) mice and patients with multiple system atrophy as well as in vivo in α-synuclein fibril-injected rats. Last, first-in-human imaging demonstrated [11C]MODAG-005 binding in brain regions affected by α-synuclein pathology in patients with clinically established MSA cerebellar type, MSA cerebellar and parkinsonian type, and Parkinson's disease."

First-in-human • Journal • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

De Novo developing nanoplatform encapsuling α-arbutin and α-syn inhibitor for precise treatment of Parkinson's disease. (PubMed, Colloids Surf B Biointerfaces) - "In present study, we developed one nanoplatform encapsuling natural antioxidant (α-arbutin) and α-synuclein inhibitor (Anle138b) for precise treatment of PD by blood brain barrier (BBB) penetrating peptide facilitated intra brain delivery...In summary, by targeting multiple pathological features of PD, we developed one multiple functional nanoplatform for that effectively mitigated PD phenotypes. Our study paves the way for precise intervention of neurodegenerative diseases by leveraging the nanomaterials facilitated delivery of natural medicine and chemical compounds."

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

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

Trial initiation date • CNS Disorders • Movement Disorders • Multiple System Atrophy

Coordination of Anle138b to Silver Results in Selective Reduction of a C-Terminal Truncated α-Synuclein Protein and Increased Aggregate Size. (PubMed, ChemMedChem) - "Using two different anti-α-synuclein antibodies, our data suggest 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 • Movement Disorders • Parkinson's Disease

INTERFERING THE AGGREGATION PROCESS OF THE C-TERMINAL DOMAIN OF TDP-43 (ADPD 2026) - "The observed interaction between CTD-TDP-43 and ANLE138b warrants further investigation. Future work will focus on exploring the molecular mechanism of this interaction in greater detail and validating these findings through solution NMR experiments. Bibliography 1."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Parkinson's Disease • TARDBP

NEUROPROTECTIVE EFFECTS OF THE INHIBITORS OF ALPHA-SYNUCLEIN AGGREGATION AND ER STRESS IN PARKINSON'S DISEASE ORGANOID MODEL (ADPD 2026) - "The main objective of the present study was to assess the potential therapeutic effect of the small-molecule inhibitors of α-syn aggregation (anle138b) and PERK signaling pathway (AMG44) against neurodegeneration in PD. The study was performed in a novel 3D in vitro model of PD... Combination of the selected α-syn and ER stress inhibitors is effective against neurodegeneration in the organoid model of PD. The obtained results could help develop the first targeted therapy for PD. This work was supported by the PRELUDIUM BIS 3 grant no."

CNS Disorders • Movement Disorders • Parkinson's Disease

TV56286-NDG-20041: An Open-Label Extension, Multi-Centered, Phase 2 Trial of TEV-56286 (Emrusolmin) for Multiple System Atrophy (clinicaltrialsregister.eu) - P1/2 | N=149 | Not yet recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC

New P1/2 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy

Modulation of α-Synuclein Oligomer and Aggregate Populations by pH and Metal Ions. (PubMed, Biomolecules) - "Anle138b increased the abundance of oligomeric species at low pH, whereas EGCG produced divergent effects at pH 5 and pH 3. We further examined the effects of metal ions, finding that Fe3+ stabilized higher-order assemblies under acidic conditions, Cu2+ delayed assembly at pH 5 while enhancing aggregation at pH 3, and Zn2+ increased oligomerization primarily at low pH. Overall, these results demonstrate that α-syn assembly is highly sensitive to coupled effects of pH, metal chemistry, and time."

Journal • CNS Disorders

TOPAS-MSA: A Trial to Test if TEV-56286 is Effective for Treatment of Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=350 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D LLC | N=200 ➔ 350 | Trial completion date: Jun 2027 ➔ Sep 2027 | Trial primary completion date: May 2027 ➔ Sep 2027

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Multiple System Atrophy

The host-guest inclusion complex of Anle 138b with Methyl-β-cyclodextrin: In vitro characterization and possible formulation development for anti-Parkinson application. (PubMed, Int J Pharm) - "Finally, the in vitro Thioflavin T assay evidenced that the Anle 138b/Me-β-CD ICX showed efficacy equal to, if not superior to, the free Anle 138b concerning the inhibition of α-syn aggregation. Definitely, it appears that solid dosage forms based on ICX could be promising for anti-PD application."

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

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