The Québec Consortium for Drug Discovery (CQDM)

CQDM PUTS THE NEEDS

of the pharmaceutical industry front and centre

The Québec Consortium for Drug Discovery (CQDM) now has two years of experience under its belt. Established in 2008, it set out to put the needs of the pharmaceutical industry front and centre, while at the same time looking for ways to allow both the public sector and the pharmaceutical industry to invest more into R&D and increase the productivity of its investments in Canada.

In order to fulfi ll these needs the CQDM created a funding program that is designed to support the development of promising new generation technologies that have the potential to transform biopharmaceutical research. The competition invites researchers from industry and academia to put forth a unique project idea and create tools and technologies to accelerate the drug discovery process.

So for the second year in a row, the CQDM has now initiated four outstanding research projects resulting from its annual competition.

“What we’re hoping to do is keep our research agenda very broad and we want to make sure we have strong projects that will have an impact on biopharmaceutical research,” said Diane Gosselin, vice president, Research and Business Development, CQDM. “As long as the projects are addressing a crucial challenge that the industry is facing right now, and as long as the project will come up with clear applicable results right away, we are satisfi ed with that.”

Here is a brief description of the projects that have been initated:

Project: A new biosensor paradigm for continuous detection of multiple analytes Principal Investigator: Emanuel Escher, Université de Sherbrooke

The capacity to monitor selected drugs, analytes or biomarkers in living organisms is crucial for drug discovery and

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the future of healthcare. It allows the monitoring of biological response during in vivo animal experimentation with minimal animal sacrifice and discomfort as well as a reduction in cost and development time. In a clinical setting it also improves the accuracy and rapidity of diagnosis and permits ultimately the implementation of personalized medicine approaches and the development of artificial organs such as an artificial pancreas for the optimal control of diabetes.

The proposed project involves the development and validation of a new generation biosensor that offers unique and broadly applicable capabilities, combining the capacity to monitor several analytes simultaneously in real time, for use ex vivo and in vivo. Relying on the evanescent field-based detection of the fluorescence of Quantum dots, the proposed biosensor brings together expertise in electrical engineering, physics, pharmacology, chemistry and physiology. As a first step, the integration of the various components will provide a pHactuated biosensor. In a next step, it will be optimized for the individual detection of glucose and insulin.

Project: A novel phage-based screening technology for antivirals Principal Investigator: Matthias Götte, McGill University

Infection with herpesviruses is associated with important human diseases including the development of cancers. Temporal or permanent deficiencies in the immune system can facilitate infection with these viruses. Patients who receive organ transplants are considered to be the most vulnerable population. Ideally, those individuals are treated with antiviral agents to prevent infection.

Unfortunately, the use of approved drugs is often associated with severe side effects, the development of drug resistance and a limited spectrum of activity against the various members of the herpesvirus family. Thus, there is an urgent medical need to discover and to develop novel anti-herpetic agents. However, technical obstacles have hampered the development of effective drugs against many of these viruses. Here we propose to dvelop a surrogate system that takes advantage of the structural and functional similarities among viral DNA polymerases and their orthologs in phages. The central hypothesis is that phage-derived chimeric polymerases containing critical parts of the substrate binding site of the viral enzyme can be used to identify novel classes of compounds that inhibit essential functions of the virus.

Project: Profiling of patients with major psychiatric disorders using electroretinography Principal Investigator: Michel Maziade, Centre de Recherche Université Laval Robert-Giffard (CRULRG) and Neuropsychiatrie Découverte et Innovation Inc. (NDEI)

The scientific basis underlying the diagnosis of schizophrenia, bipolar disorder and major depression is unclear. This generates uncertainties about the classification of patients in clinical research settings and for efficacious treatment. We propose a novel approach, based on the use of electroethinography, which measures the response of the retina to light stimulation. The retina, as part of the central nervous system, constitutes a powerful site of investigation for understanding brain disorders such as schizophrenia.

Previous work by Maziade and Hébert supports this approach and the changes in electroretinography observed in patients reflect a disturbance in the chemistry of the brain. Using this approach, we propose to develop an array of biomarkers that will tag the different sub-groups of patients within these diseases, both at the stage of the disease and in the years preceding its onset.

Project: Integrated platform to identify synthetic lethality opportunities in cancer therapy Principal Investigator: Gordon Shore, McGill University and Gemin X Pharmaceuticals Inc.

Basic research has made important advances in understanding the causes of cancer resulting in the discovery of a new generation of therapeutic drugs targeted to specific malfunctions in cancer cells. However, each cancer type represents a unique disease, which harbours a variety of genetic mutations allowing cancer cells to grow and

develop resistance to many current therapies. Typically, these hurdles are addressed by confucting a large number of human clinical trials with a wide variety of patients and drug combinations, a process which often requires

several years before determining which patients will ultimately benefi t.

One approach to address this issue is the concept of synthetic lethality, which refers to the identity of two genes that when eliminated individually are unobtrusive to the cancer cell, but together their elimination results in cell lethality. In cancer therapy, this can be achieved either by combining two or more drugs chosen to stop the function of the two synthetically lethal genes or by selecting patient populations that harbour a tumour mutation that allows enhanced responsiveness to a specifi c drug. The 2010-2011 competition is now underway, with the deadline for the submission of the letters of intent being Oct. 25. In 2010-2011, CQDM will fund three to fi ve innovative projects for up to $2 million per project.

Looking ahead

The 2010-2011 competition is now underway, with the deadline for the submission of the letters of intent being Oct. 25. In 2010-2011, CQDM will fund three to five innovative projects for up to $2 million per project. CQDM’s funding will be awarded following a competitive process in two stages.

The selection of the letters of intent will be overseen by the CQDM’s Strategic Orientation Committee. Only applicants whose letter of intent will be selected will be invited to submit a full project proposal before Feb. 14, 2011.

Evaluation of the proposals will involve an international peer review led by the Fonds de la recherche en santé du Québec (FRSQ) and a risk analysis performed by CQDM. Announcement of the final selection will be made in April 2011.

For a complete description of the 2009-2010 projects that have been initiated, please visit the CQDM website at www.cqdm.org.

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