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Assay for AD
TORONTO—Amorfix Life Sciences Ltd. will work with QPS Holdings LLC, a global provider of discovery and development services for pharmaceutical, biotechnology and medical device companies, to further develop and validate its proprietary Alzheimer's disease (AD) diagnostic EP-AD assay.
The companies will work together to obtain and analyze cerebrospinal fluid (CSF) samples from a variety of Alzheimer's disease patients in various stages of disease. Amorfix and QPS will perform the studies necessary to validate and ultimately commercialize the EP-AD assay for use as both a biomarker to facilitate clinical development of new treatments for AD, and a U.S. Food and Drug Administration (FDA)-approved early-stage diagnostic test for AD. QPS will provide samples from a variety of sources, and Amorfix will work to transfer the technology to their group where eventually the assay will be run on a regular basis.
"We are looking forward to working with QPS to validate our EP-AD assay," says Dr. Robert Gundel, Amorfix's president and CEO. "Our studies using the EP-AD assay demonstrate that it is able to identify early-stage patients with mild cognitive impairment with a sensitivity of 94, which is higher than the sensitivity achieved with other biomarkers used as comparators in the same study. AD is one of the most active areas of therapeutic development, with more than 93 new treatments being evaluated in clinical studies. We believe that with QPS, we can bring the EP-AD assay to market quickly for use with any or all 93."
Gundel explains why he is optimistic: "We use our ProMIS Discovery Platform to identify what we call 'disease-specific epitopes,' or DSEs. It is a computer-based algorithm that, based on a thermodynamic analysis of the protein three-dimensional structure, predicts where proteins are most likely to partially unfold or be misfolded. When a protein is partially unfolded, it exposes areas of the protein that are normally hidden or buried in the three-dimensional structure and, therefore, not available as epitopes for monoclonal antibody binding. In this way, we identify these DSEs and then use these small peptides as immunogens to generate specific monoclonal antibodies which will bind only to the misfolded or partially unfolded version of the protein and not to the natively folded protein."
Amorfix's working hypothesis is that molecules such as cell surface receptors are expressed on the cell surface of tumor cells. The tumor microenvironment is slightly acidic and flooded with free radicals and other destructive molecules forming conditions right for the partial denaturing (causing partial unfolding) of proteins, thereby creating a situation where partially unfolded cell surface receptors are expressed on tumors and not normal cells.
"We have proven this hypothesis with many different molecules and validated our discovery platform," Gundel says. "This is a unique and novel approach to the generation and development of targeted therapeutics, and we now have antibodies for each of our programs that only bind and kill tumor cells, and do not bind or kill normal cells. No one else in the world is doing anything like this."
The relationship with QPS came about through Amorfix's AD diagnostic work, Gundel notes.
"We developed a preclinical test to measure aggregated Abeta oligomers—the building blocks of the plaque that forms in the brains of Alzheimer's disease patients—and were offering this as a tool that Big Pharma and academics could use to accelerate preclinical development of new therapeutics for the treatment of AD," he says. "Using this tool, one can get an answer as to whether or not an experimental treatment is actually reducing the levels of Abeta oligomers and plaque formation in the brain in a couple of months, compared to 12 to 18 months using conventional immunohistochemical methods. QPS has a big presence in neurodegenerative diseases, and they were very interested in licensing the technology to have it as part of their package of services."