TORONTO—Amorfix Life Sciences Ltd. will work with QPSHoldings LLC, a global provider of discovery and development services forpharmaceutical, biotechnology and medical device companies, to further developand validate its proprietary Alzheimer's disease (AD) diagnostic EP-AD assay.
The companies will work together to obtain and analyzecerebrospinal fluid (CSF) samples from a variety of Alzheimer's diseasepatients in various stages of disease. Amorfix and QPS will perform the studiesnecessary to validate and ultimately commercialize the EP-AD assay for use asboth a biomarker to facilitate clinical development of new treatments for AD,and a U.S. Food and Drug Administration (FDA)-approved early-stage diagnostictest for AD. QPS will provide samples from a variety of sources, and Amorfixwill work to transfer the technology to their group where eventually the assay willbe run on a regular basis.
"We are looking forward to working with QPS to validate ourEP-AD assay," says Dr. Robert Gundel, Amorfix's president and CEO. "Our studiesusing the EP-AD assay demonstrate that it is able to identify early-stagepatients with mild cognitive impairment with a sensitivity of 94, which ishigher than the sensitivity achieved with other biomarkers used as comparatorsin the same study. AD is one of the most active areas of therapeuticdevelopment, with more than 93 new treatments being evaluated in clinicalstudies. We believe that with QPS, we can bring the EP-AD assay to marketquickly for use with any or all 93."
Gundel explains why he is optimistic: "We use our ProMISDiscovery Platform to identify what we call 'disease-specific epitopes,' orDSEs. It is a computer-based algorithm that, based on a thermodynamic analysisof the protein three-dimensional structure, predicts where proteins are mostlikely 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 thethree-dimensional structure and, therefore, not available as epitopes formonoclonal antibody binding. In this way, we identify these DSEs and then usethese small peptides as immunogens to generate specific monoclonal antibodieswhich will bind only to the misfolded or partially unfolded version of theprotein and not to the natively folded protein."
Amorfix's working hypothesis is that molecules such as cellsurface receptors are expressed on the cell surface of tumor cells. The tumormicroenvironment is slightly acidic and flooded with free radicals and otherdestructive molecules forming conditions right for the partial denaturing(causing partial unfolding) of proteins, thereby creating a situation wherepartially unfolded cell surface receptors are expressed on tumors and notnormal cells.
"We have proven this hypothesis with many differentmolecules and validated our discovery platform," Gundel says. "This is a uniqueand novel approach to the generation and development of targeted therapeutics,and we now have antibodies for each of our programs that only bind and killtumor cells, and do not bind or kill normal cells. No one else in the world isdoing anything like this."
The relationship with QPS came about through Amorfix's ADdiagnostic work, Gundel notes.
"We developed a preclinical test to measure aggregated Abetaoligomers—the building blocks of the plaque that forms in the brains ofAlzheimer's disease patients—and were offering this as a tool that Big Pharmaand academics could use to accelerate preclinical development of newtherapeutics for the treatment of AD," he says. "Using this tool, one can getan answer as to whether or not an experimental treatment is actually reducingthe levels of Abeta oligomers and plaque formation in the brain in a couple ofmonths, compared to 12 to 18 months using conventional immunohistochemicalmethods. QPS has a big presence in neurodegenerative diseases, and they werevery interested in licensing the technology to have it as part of their packageof services."