Alzheimer’s Disease

A Potential Best-in-Class Therapy for Alzheimer’s Disease

ProMIS’ lead therapeutic program, PMN310, is a monoclonal therapeutic antibody designed for the treatment of Alzheimer’s disease (AD). By selectively targeting the toxic oligomers of amyloid-beta (Aβ), PMN310 may possess the qualities necessary to potentially be “best-in-class”, with a possibly improved clinical safety and efficacy profile over other amyloid-directed antibody therapeutics currently in clinical development.

Three Forms of Amyloid Protein

  • Monomers - Simple strings of amino acids that play a role in normal brain health.
  • Oligomers - Small clumps of molecules that consist of several monomer units.
  • Plaque - Insoluble, solid deposits of amyloid (similar to plaque in arteries) that can build up over time. Usually present, but does not appear to play a significant role in disease progression.

The Right Target

Only misfolded oligomers are toxic, which can lead to neuronal death and synaptic loss that causes AD-related cognitive decline. Studies indicate that safe and effective antibody therapies for AD will be those that selectively target and bind only to misfolded oligomers while avoiding any binding to monomers and/or plaque forms of amyloid.

Misfolded Protein Targets for Alzheimer’s

Misfolded Protein Target Lead Indication Other Indications Status
Amyloid-beta Alzheimer’s IND Enabling Work Ongoing
Tau Alzheimer’s PSP, Other Tauopathies Lead Selection

PMN310 Key Features

Our PMN310 program is a next-generation, best-in-class anti-amyloid therapy.

  • Highly selective for only misfolded, toxic oligomers
    • Does not bind monomer
    • Does not bind plaque or vascular deposits
      • Likely no amyloid-related imaging abnormality-edema (ARIA-E) (brain swelling) side effect
  • Doses expected not to be limited by off-target binding or side effects
  • All dosed PMN310 will be focused on neutralizing toxic oligomers
    • Potentially greater clinical efficacy

Screening and Validation for PMN310

Identifying Toxic Oligomers of Amyloid

PMN310 was designed using our proprietary technology platform to target only the toxic form of amyloid-beta (Aβ). Six different conformational epitopes were identified that were predicted to be exposed only on the surface of toxic oligomers of amyloid. Our scientists then created six peptide antigens that mirrored those epitopes and immunized mice with the newly developed antigens.

The immune systems of these mice created multiple antibody candidates that were screened for selectivity, preclinical efficacy, and binding to biological samples from patients (cadaveric brain material from patients who died from AD). From this extensive screening process, PMN310 emerged as the lead antibody candidate.

Targeting Only the Most Neuropathogenic Aβ Species

PMN310’s selectivity for the toxic oligomer form of amyloid indicates that it may possess the features necessary to be considered a potentially “best-in-class” treatment for AD, possibly with an improved clinical safety and efficacy profile over other antibody therapeutic candidates currently in development. PMN310’s lack of off-target binding to Aβ plaque, which has been associated with a high incidence of ARIA-E, also strongly suggests a potential safety advantage.

PMN310: Potential for Value-creating Clinical Data

2021
2022
2023
Aducanumab Approval June 7 2021
Aducanumab Launch and Market Development
BAN2401 Ph 3 data
BAN2401 Potential approval
ProMIS
Final IND enabling work
Sporadic AD Phase 1: 3 month Placebo controlled, 9 month extension, Multiple Ascending Dose (MAD) design
Open label after 3 months of treatment
Ongoing biomarker readouts could provide signal of treatment effect

Recent advances in blood-based biomarkers may allow us to detect an objective treatment signal as early as Phase 1, potentially providing rapid and cost-effective proof-of-concept.

  • 2021 - 2022

    • ProMIS Final IND enabling work
  • 2023

    • Sporadic AD Phase 1: 3-month placebo-controlled, 9-month extension, MAD design
    • Open-label after 3 months of treatment
    • Ongoing biomarker readouts could provide signal

Development Status

Upon completing producer cell line development for PMN310, we will complete the further preclinical work necessary (including a good manufacturing practice (GMP) compliant manufacturing dossier) to enable us to submit an Investigational New Drug (IND) application to the FDA to approve PMN310 for Phase 1 clinical testing in humans in the U.S.

Devising a Safe and Effective Alzheimer’s Vaccine

Through the strategic use of disease-associated epitopes identified through our proprietary discovery platform, we aim to devise a safe and effective vaccine to induce a specific immune response against toxic Aβ oligomers (AβOs). An AD vaccine capable of inducing an effective antibody response against pathogenic Aβ could be administered as a preventative measure to at-risk individuals to prevent the development of symptomatic disease or given therapeutically to diagnosed patients to inhibit the progression of AD. ProMIS is collaborating with the Vaccine and Infectious Disease Organization (VIDO) of the University of Saskatchewan to conduct preclinical vaccine development.

TDP-43 Antibody Therapies for ALS

Research shows misfolded TAR DNA-binding protein 43 (TDP-43) is implicated in the development of amyotrophic lateral sclerosis (ALS). Our ALS therapeutic programs target these toxic misfolded forms of TDP-43 and have shown potential benefits in combating disease progression.

Alpha-synuclein Programs for Parkinson’s

Studies indicate that alpha-synuclein (α-Syn) plays a key role in the development of Parkinson’s disease (PD) and other neurodegenerative disorders. Our therapeutic program candidates have shown high selectivity for misfolded α-Syn and potential benefits in reducing the neurotoxicity and propagation of misfolded α-Syn.

Scientific Posters & Publications

Our scientific expertise is backed by decades of research on protein misfolding diseases such as AD, ALS, and PD. We encourage you to visit our scientific library to learn more about our programs.

View Posters & Publications