Challenges in targeting
The central challenge in targeting misfolded
proteins for therapeutic effect is a product’s ability to differentiate, or conformationally select, between a misfolded
protein and a normally-folded protein. This ability to conformationally select for the misfolded protein prevents the therapeutic
candidate from interfering with the function of the normally-folded protein, thereby reducing the risk of side effects.
Benefits of our approach
The key aspect of both our SupraAntigen
and Morphomer technology platforms is conformational specificity, which we believe is central to the development of effective and
safe therapeutics for neurodegenerative diseases. Our SupraAntigen platform targets misfolded proteins through antigens displayed
on the surface of liposomes which mimic the targeted pathological form of the protein. In a complementary approach, our Morphomer
platform uses small molecular weight compounds to target the aggregation and seeding process, which prevents the misfolded proteins
from aggregating inside the cell and the formation of new misfolded proteins in healthy neighboring cells through a seeding mechanism.
Small molecules derived from our Morphomer platform, which we refer to as Morphomers, also promote disaggregation of already formed
pathological protein aggregates.
The diagram above shows how we believe
our therapies aim to intervene in the key pathology steps involved in neurodegenerative diseases: (1) prevent misfolding;
(2) promote disaggregation; (3) inhibit spreading; and (4) prevent seeding in healthy cells.
Current Treatment Paradigm for Neurodegenerative
Current diagnostic and treatment paradigms
for neurodegenerative diseases are suboptimal. Diagnosis typically takes the form of observation of cognitive, functional and behavioral
impairment and other symptoms of the diseases, which are generally only apparent after irreversible neuronal damage has already
occurred. These symptoms are treated with medicines capable of providing cognitive benefit and functional improvement but fail
to affect the progression of the disease. For AD, there are currently four approved therapies, all of which only provide modest
efficacy in treating the symptoms of AD, while having significant side effect risks, and fail to address the progression of the
disease. Despite these shortcomings, marketed therapies, such as Eisai and Pfizer’s Aricept, have achieved peak annual global
sales of approximately USD 4 billion prior to loss of exclusivity. Similarly, in the treatment of PD, the current standard
of care is intended only to alleviate physical symptoms. In both AD and PD, there are no approved disease-modifying treatments
that slow or stop the course of disease progression.
Modifying the progression of the disease
requires targeting the underlying biological processes that drive disease progression. Unfortunately, these processes evolve over
the course of many years prior to manifestation of symptoms and a high percentage of neurons may be lost prior to clinical manifestation.
Many of the failed clinical studies for disease-modifying treatments targeted patients with moderate stages of the disease, when
irreversible neuronal damage and death had already occurred. This has led to the conclusion that early intervention is necessary
to slow the disease progression and that disease-modifying therapies should be studied in patients with milder stages of the disease.
As a result of this, in recent years, there has been a movement towards early intervention in clinical development. Early intervention,
however, requires accurate disease detection prior to physical manifestation of symptoms, using new and sophisticated technologies
that are superior to the subjective rating scales currently used to assess patients. Thus, new diagnostic technologies are critical
to the clinical development process of disease-modifying therapies and ultimately better disease management of patients with neurodegenerative