PMN267 / ProMIS Neurosci - LARVOL DELTA

Key Pipeline Programs (GlobeNewswire) - "PMN267 is a humanized IgG1 antibody directed against toxic misfolded TDP-43 as a potential therapeutic target for ALS and is ready to progress to IND-enabling studies....PMN442 is a humanized IgG1 antibody and is ProMIS’s lead candidate for PD, MSA and other synucleinopathies based on its selective binding and protective activity against pathogenic forms of alpha-synuclein and is ready to progress to IND-enabling studies."

Preclinical • Amyotrophic Lateral Sclerosis • Multiple System Atrophy • Parkinson's Disease • Tauopathies And Synucleinopathies

ProMIS Neurosciences Publishes in the Journal of Biological Chemistry on the Interaction Between Pathogenic Proteins as a Treatment Target for ALS (GlobeNewswire) - "ProMIS Neurosciences Inc...today announced the publication of supportive preclinical data in the Journal of Biological Chemistry....ProMIS is developing antibodies selectively targeting misfolded forms of TDP-43 and SOD1....The study demonstrated a pathologic synergy between SOD1 and TDP-43 in cell culture and in zebra fish.The interaction between these 2 proteins was characterized at the molecular level.The results indicated that the misfolded TDP-43 epitope previously identified by ProMIS and targeted by PMN267 contains a tryptophan amino acid critical to the pathogenic interaction with SOD1 thereby providing further biological support for the potential of therapeutic intervention with PMN267."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

RACK1 Knockdown Alleviates TDP-43-Associated Global Translational Suppression in vitro, and Neurodegeneration in vivo (AAN 2022) - "Our results suggest that RACK1 knockdown represents a viable approach to alleviate the detrimental effects of TDP-43 proteinopathy without apparent adverse effects."

Preclinical • CNS Disorders • Proteinopathy • RACK1 • TARDBP

[VIRTUAL] Selective targeting of intracellular misfolded, pathogenic TDP-43 with rationally designed intrabodies (AAIC 2021) - "Immunization with an NTD epitope of misfolded TDP-43 gave rise to mAbs selective for pathogenic vs physiologically important forms of TDP-43. Intrabody constructs derived from these mAbs were able to promote clearance of intracellular pathogenic TDP-43 without toxicity to the cells."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Immunology • TARDBP

[VIRTUAL] Precision Immunotherapies for Protein Misfolding Diseases to Advance ALS & FTD Therapeutics (CNSS 2021) - "Synopsis Exploring how the ProMIS Platform is being leveraged to develop protein misfolding-specific immunotherapies for neurodegeneration Case study: selective targeting of toxic forms of TDP-43 in ALS and FTD, while sparing normally folded functional TDP-43 Dissecting the role of prion-like propagation of misfolded proteins in neurodegeneration"

Alzheimer's Disease • CNS Disorders • Proteinopathy • TARDBP

[VIRTUAL] Targeting of misfolded, pathogenic TDP-43 with rationally designed antibodies (AAIC 2020) - "Immunization with an NTD epitope of misfolded TDP-43 gave rise to mAbs selective for pathogenic vs physiologically important forms of TDP-43. The mAbs were capable of inhibiting cell-to-cell propagation of misfolding TDP43 in vitro. Such antibodies may have value against extracellular transmission of misfolding TDP-43 or as pathogenic TDP43-specific intrabodies expressed intracellularly."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Dementia • Frontotemporal Lobar Degeneration

Generation of Antibodies Selective for Misfolded Disease-associated TDP-43 (AAN 2020) - "We have found that a tryptophan (Trp68) in the TDP-43 N-terminal domain (NTD) participates in the cross-seeding of SOD1 misfolding propagation (Pokrishevsky et al, submitted), despite being inaccessible in the natively folded NTD (e.g., Afroz et al, Nature Comm 2017). We have developed a family of antibodies sensitive to solvent exposure of NTD Trp68 that are selective for misfolded/aggregated, disease-associated TDP-43 while sparing physiologically important molecular species, which may find utility in biomarker and immunotherapy applications for TDP-43 associated diseases."

IO Biomarker • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Proteinopathy • Tauopathies And Synucleinopathies

ProMIS Neurosciences creates novel intrabodies for ALS, frontotemporal dementia and other neurodegenerative diseases (GlobeNewswire, ProMIS Neurosciences Inc.) - "ProMIS Neurosciences…has generated intrabodies highly selective for misfolded forms of TAR DNA-binding protein 43 (TDP-43) implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and several other neurologic disorders. Early data support the use of these intrabodies within gene therapy vectors based on their selectivity and ability to promote degradation of toxic species of TDP-43 while preserving normal forms of the protein."

Biomarker • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy • Rare Diseases • Tauopathies And Synucleinopathies

Journal of the American Academy of Neurology Publishes ProMIS Neurosciences’ Abstracts on Novel Antibody Candidates (GlobeNewswire, ProMIS Neurosciences Inc.) - "ProMIS Neurosciences, Inc....demonstrate the strength of its antibody programs for Parkinson’s disease/alpha-synuclein (a-syn) and amyotrophic lateral sclerosis (ALS)/TDP-43....The abstract...demonstrates the success of the ProMIS discovery platform in identifying disease-associated targets and generating antibodies against the toxic species of a-syn while preserving the healthy protein. The misfolded form of a-syn is implicated in the development of Parkinson’s disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).... Abstract reveals a family of antibodies reactive with a defined region of TDP-43 that becomes exposed on misfolded/aggregated, disease-associated TDP-43 but not on the properly folded healthy protein. Pathogenic TDP-43 is a recognized driver of ALS and frontotemporal lobar dementia (FTLD)."

Clinical • Preclinical

Data showing precision selectivity for neurotoxic TDP-43 and alpha-synuclein publishes in Neurology (GlobeNewswire) - "ProMIS Neurosciences...announced today that the journal Neurology will publish AAN abstracts of data that demonstrate the strength of its antibody programs for Parkinson’s disease/alpha-synuclein (a-syn) and amyotrophic lateral sclerosis (ALS)/TDP-43. The data will appear in the April 14 online supplement to Neurology, the most widely read, highly cited peer-reviewed neurology journal."

Clinical data