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.

Our Pipeline

We are developing a pipeline of antibodies aimed at selectively targeting misfolded toxic forms of proteins that drive neurodegenerative diseases without interfering with the essential functions of the same properly folded proteins.

Product candidate / Target Protein	Indication	Discovery	Pre-clinical	Clinical
Product candidate / Target Protein	Indication	Discovery	Pre-clinical	Phase 1	Phase 2	Phase 3
PMN310 / Amyloid-beta	AD	Discovery Phase complete	Pre-clinical Phase complete	Phase 1 Phase in progress	Phase 2 Phase not started	Phase 3 Phase not started
PMN267 / TDP-43	ALS	Discovery Phase complete	Pre-clinical Phase in progress	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started
PMN442 / Alpha-synuclein	MSA	Discovery Phase complete	Pre-clinical Phase in progress	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started

The company plans to investigate additional synucleinopathies, including PD and DLB.

Additional Developement Programs

Target Protein	Role of normal form of the protein	Disease Indication	Discovery	Pre-clinical	Clinical
Target Protein	Role of normal form of the protein	Disease Indication	Discovery	Pre-clinical	Phase 1	Phase 2	Phase 3
RACK 1	Protein synthesis	ALS1, HD	Discovery Phase in progress	Pre-clinical Phase not started	Phase 1	Phase 2	Phase 3	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started
Tau	Microtubule stabilization, neurite development	Alzheimers's1, FTLD, PSP, CBD	Discovery Phase in progress	Pre-clinical Phase not started	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started
SOD 1	Anti-oxidant activity, glucose metabolism	ALS	Discovery Phase in progress	Pre-clinical Phase not started	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started
DISC1 + interactome	Neurogenesis, mitochondrial transport	Schizophrenia	Discovery Phase in progress	Pre-clinical Phase not started	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started
Amyloid Vaccine	Synaptic plasticity, memory formation	Alzheimer's prevention	Discovery Phase in progress	Pre-clinical Phase not started	Phase 1 Phase not started	Phase 2 Phase not started	Phase 3 Phase not started

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

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

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

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

PMN267: 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

PMN442: Drug candidate being developed for Multiple System Atrophy (MSA) designed to selectively target and protect against pathogenic a-syn species.

About our MSA Program

Alpha-synuclein Program for Multiple System Atrophy

PMN442: Drug candidate being developed for Multiple System Atrophy (MSA) designed to selectively target and protect against pathogenic a-syn species.

About Our MSA Program