Product Pipeline

Developing Next-generation Treatments to Fight Neurodegenerative and Other Misfolded Protein Diseases

At ProMIS Neurosciences, we use state-of-the-art, proprietary computational modeling to predict and identify specific targets (epitopes) expressed on the molecular surface of toxic oligomers (misfolded proteins), which are known root causes of several neurodegenerative and other misfolded protein diseases. These oligomers are toxic to neurons and can spread throughout the brain or spinal cord, killing neurons, and leading to the development and progression of neurodegenerative and other misfolded protein diseases.

A Growing Portfolio of Selective Antibody Therapies

Misfolded Protein Target Lead Indication Other Indications Status
Amyloid-beta Alzheimer’s IND Enabling Work Ongoing
TDP-43 ALS FTD, LATE Lead Antibodies
Alpha-synuclein Multiple System Atrophy Parkinson’s, DLB Lead Antibodies
Tau Alzheimer’s PSP, Other Tauopathies Lead Selection
SOD1 ALS Lead Antibodies
RACK1 ALS HD, Cancers Antibody Screening
Ataxin2 ALS Immunizations
Disc1 Schizophrenia Computational Modeling
Amylin T2 Diabetes Computational Modeling

DLB: Dementia with Lewy bodies
FTD: Frontotemporal dementia
LATE: Limbic-predominant age-related TDP-43 encephalopathy
ALS: Amyotrophic lateral sclerosis

PSP: Progressive supranuclear palsy
AD: Alzheimer’s disease
HD: Huntington’s disease

A Rigorous Screening and Validation Process

Our process for selecting the best-in-class product candidates begins with the identification of epitopes expressed only on the surface of toxic oligomers. Murine monoclonal antibodies (mAbs) are raised against these targets and evaluated in a 3-step process to identify the best products to take into clinical development. This immunization strategy produces antibodies with the desired selective binding profile.

Initial Screening for Binding

Initial Screening for Binding

During initial screening for binding, we observe and identify the mAbs that show selective binding to the toxic oligomers and do not bind to the non-toxic forms of the relevant protein. Once the top candidates are selected, they move on to the validation phase.

Functional Assays

Functional Assays

Among the validated product candidates, we use two complementary sets of assays to identify those that demonstrate evidence for blocking of neurotoxicity (killing of neurons) and inhibition of propagation (spreading throughout the brain). Only validated products that meet these criteria can move on to undergo testing in animal models to confirm their therapeutic potential.

Final Validation and Selection

Final Validation and Selection

In parallel, the binding profiles of the antibody candidates are evaluated using postmortem brain samples from patients. Those that show significant binding to toxic oligomers in brain samples are selected for further development.

PMN310: A Potential Next Generation Therapy for Alzheimer’s Disease

Our leading therapeutic program, PMN310, is a monoclonal antibody that selectively binds to the toxic misfolded forms of amyloid-beta, a protein commonly associated with the development of Alzheimer’s disease. In preclinical studies, PMN310 has shown significantly greater selectivity for toxic oligomers in AD brain samples than has been shown with other amyloid-directed antibody therapies currently in clinical development.

About PMN310 for Alzheimer’s

TDP-43 Targeted Therapies for ALS

The formation of misfolded TAR DNA-binding protein 43 (TDP-43) aggregates inside neurons has been associated with the development of amyotrophic lateral sclerosis (ALS). We have several lead program candidates that have shown the desired selectivity for misfolded TDP-43, and initial functional benefits in clearing aggregated TDP-43 from cells.

About Our ALS Programs

Alpha-synuclein Programs for Parkinson’s Disease

Studies show that alpha-synuclein (α-Syn) plays a major role in the development of Parkinson’s disease and other neurodegenerative disorders. We are working to identify program candidates that show high selectivity for misfolded α-Syn, and initial functional benefits in reducing the neurotoxicity and propagation of misfolded α-Syn.

About Our Parkinson’s Programs