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Cardiovascular Biomarker Translation (CBT) program

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Overview

Heart failure (HF) is the most costly chronic disease in developed and developing countries. More than 26 million people worldwide are suffering from HF, placing great stresses on patients, caregivers and health care systems. The number of patients will be increasing in the next decades due to ageing populations, therefore improved diagnosis and therapy of HF are important goals of major healthcare organizations. In keeping with its mission to identify areas of unmet medical needs and develop innovative health care solutions, Roche Diagnostics is partnering with the University of Ottawa Heart Institute (UOHI) to develop a better way to identify and classify HF, based on testing novel biomarkers for the disease. To date, with previous Genome Canada funding, UHOI, University of Toronto and Roche Diagnostics have identified eight novel biomarker candidates for HF characterization and have filed for global patents for these candidates. Now, the partners will conduct further clinical evaluation of the biomarkers, with the intent of developing a HF biomarker panel and an accompanying clinical development program to translate the findings from basic research to clinical benefit of patients. Partnering with Roche has the strategic advantage that their diagnostic test might run on more than 40,000 Roche Diagnostic instruments worldwide. The Panel aims to assist physicians in earlier identification and classification of HF and support personalized HF treatment that might result in more effective therapies and better outcomes for HF patients. These are important aspects in view of patient burden and costs associated with HF, with particular focus on minimizing length of hospitalization, re-admissions, unnecessary treatments and adverse events. The project aims at promoting Canadian leadership in medical innovation and attracts additional partnerships and investments from major leaders in the global biotech industry.

Developing Vasculotide, a genomic/proteomic-derived treatment to target vascular inflammation and destabilization

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Overview

More than one million cardiac surgeries are carried out each year, usually successfully. Nearly one-third of high-risk patients, however, will experience a rapid loss of kidney function after surgery, known as Acute Kidney Injury, or AKI. AKI is the result of short-term interruptions in blood flow during surgery; 11 percent of patients who develop AKI after bypass surgery will die, compared to 2 percent of those who do not. Those who survive AKI are at risk of developing longer term kidney complications such as chronic kidney disease or End Stage Renal Disease. There is, therefore, a pressing need for better ways to prevent or treat AKI. Drs Dumont and Van Slyke conceptualized and designed a drug called Vasculotide (VT) that binds to the Tie2 receptor, which is responsible for maintaining vascular health (and thus blood flow). Vasomune Therapeutics, the company developing and commercializing the drug, is partnering with these researchers to develop VT to the point where it is ready for human clinical trials. At that point, Vasomune will be positioned to seek venture capital for further development. Within three-to-five years of the end of the project, Vasomune will be a venture-backed Ontario biotech company with a Phase II clinical program in renal disease. Being able to prevent or reverse AKI will save the healthcare system as much as $1 billion each year, in part because fewer patients will develop chronic kidney disease. Canadians will also have earlier access to VT. Commercializing VT will also bring financial returns to Canada and provide training and create jobs for highly qualified personnel.

Clinical utility and enhancements of a pharmacogenomic decision support Tool for Mental Health Patients

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Overview

One in five Canadians will experience some form of mental illness in their lifetime. Treatments are available but each person responds differently to them, in part because of their genes. A clinically proven genetic test, called GeneSight, analyzes an individual’s genes and recommends the optimal drugs for that person along with dose adjustments among the 33 most commonly prescribed antidepressant and antipsychotic drugs. Clinical testing in the United States has shown that GeneSight doubles the odds of a patient responding to antidepressant medication. More than 100,000 patients have received GeneSight tests in the United States. Now, Assurex Health, the company that developed GeneSight, is partnering with scientists at Toronto’s Centre for Addiction and Mental Health (CAMH) to develop the Enhanced GeneSight (E-GeneSight) genomic test. E-GeneSight will incorporate new genomic markers that scientists at CAMH have identified and characterized for their association with patient responses to psychiatric medications. Assurex Canada and CAMH will together validate these markers for their ability to predict efficacy and side effects of psychiatric medications; the most predictive markers will be integrated into E-GeneSight. E-GeneSight, when launched in 2017, is anticipated to reduce the need for “trial-and-error” approaches to prescribing and increase the likelihood that people will respond optimally to the medications prescribed for them, while reducing side effects. This will increase the proportion of patients who stay on their medications and improve their quality of life. It will also save the Canadian healthcare system $4,000 per year per treatment-resistant patient and will generate royalty revenues for CAMH as E-GeneSight is marketed internationally.

Novel rapid diagnostic tools for lung transplantation: Bringing omics to the bedside

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Overview

A considerable number of patients needing a lung transplant die due to a lack of donor organs deemed suitable for transplant. Now, a proposed genomics approach to assessing donor lungs has the potential to save thousands of lives while reducing healthcare costs. The project, led by Dr. Shaf Keshavjee of Toronto’s University Health Network (UHN) in collaboration with the U.S. biotech firm Lung Bioengineering Inc., a subsidiary of United Therapeutics Corp., intends to develop a genomics-based diagnostic test to determine whether a donor lung meets transplant requirements. At present, such evaluations are based on physiological assessments alone. As a result, less than 15 per cent of lungs, the healthiest, are deemed suitable for transplant, leaving unused countless “marginal” lungs that also could save lives. A genomics-based analysis could increase the number of transplant-acceptable lungs to nearly 50 per cent, resulting in a greater number of patients receiving this life-saving intervention. Using diagnostic test kits, donor lung conditions would be precisely monitored through biomarker analyses. Under Dr. Keshavjee’s research leadership, some biomarkers have already been isolated that can predict lung quality. Building on these findings, this new initiative will result in the creation of rapid diagnostic tools that could be used in transplant centres around the world. The world’s first successful clinical lung transplant took place at Toronto General Hospital in 1983. Today’s genome project has the potential to further cement Canada’s global leadership in this high-tech medical sector. This initiative may also reduce the economic burden on the Canadian healthcare system while improving overall quality of life for lung-transplant patients.

Toward a national framework for clinical cancer genome profiling in Canadian hospitals

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Overview

Approximately 200,000 Canadians are diagnosed with cancer each year. More than one in four of these patients can benefit from targeted treatment based on a genomic analysis of their tumours. Indeed, genome-based tumour profiling helps treat patients with the right drug at the right time, improving outcomes and saving lives. However, at present this breakthrough testing is not widely available and is currently only being used in a clinical trial setting for patients with advanced cancers at one Toronto Hospital, and its collaborators. This genomics project between Dr. Suzanne Kamel-Reid of Princess Margaret Cancer Centre (University Health Network) and LifeLabs Medical Laboratory Services, Canada’s leading diagnostic lab company, is the first step in providing national market access to this potentially vital information. In addition to saving lives, personalized cancer medicine data can reduce healthcare costs significantly, as the cost of treatment can be up to 10 times more than the cost of laboratory genomic cancer testing. Projected to total Canadian healthcare expenditures, genomic tumour profiling is expected to save the healthcare system hundreds of millions of dollars annually.

SIRPaFc: Translating genomics research into a novel cancer immunotherapy

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Overview

Nearly all (96 per cent) people aged 65 or older diagnosed with acute myeloid leukemia (AML) die within five years, as do two-thirds of younger patients. Because it primarily affects older people, the incidence of this aggressive cancer is expected to rise in coming years as the population ages. Chemotherapy regimens for AML have remained essentially unchanged since the 1970s. With standard treatment, many patients can achieve remission, but most will relapse; following relapse two-thirds of patients will die within 3 years. One of the reasons for the high rate of relapse in AML is that standard chemotherapy does not kill leukemia stem cells, leaving them to grow and mature into new leukemia cells. Leukemia stem cells express high levels of a protein called CD47. This protein sends a “do not eat” signal that stops white blood cells of the immune system called macrophages from surrounding and “eating” cancer cells. With previous support from Genome Canada and Trillium Therapeutics Inc. (TTI), a publicly traded biotech company in Toronto, Canada, Dr. Jean Wang and team at the Princess Margaret Cancer Centre, University Health Network, and Dr. Jayne Danska and team at SickKids have developed SIRPaFc, a novel therapeutic that blocks the “do not eat” signal, freeing the immune system to attack leukemia stem cells. TTI is completing formal preclinical studies and will carry out clinical trials aimed at demonstrating SIRPaFc’s safety and efficacy. The collaboration between Drs. Wang and Danska and TTI will assist in realizing the commercial potential of this promising discovery.

Preclinical development of drugs for Intracerebral Hemorrhage (ICH)

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Overview

Intracerebral hemorrhage (ICH) is a form of brain hemorrhage responsible for 10 per cent of all strokes. It affects about 90,000 people in North America each year, more than half of whom either die or are disabled. Anywhere from one-quarter to 44 per cent of those who survive have recurring ICH. The annual economic burden of ICH is estimated at $300 million to Canada and $6 billion to the United States. Apart from treating hypertension, which is one of the causes of ICH, there is currently no way to prevent recurrent ICH. Dr. Xiao-Yan Wen, director of the Zebrafish Centre for Advanced Drug Discovery (ZCADD) and his team at St. Michael’s Hospital, used genomics-driven research tools to identify several existing drugs that are already approved by the US Food and Drug Administration (FDA) that have shown the ability to prevent ICH in zebrafish models. In this project, Edge Therapeutics is partnering with Dr. Wen to perform preclinical studies on the most potent anti-ICH molecules known as EZF-0100 for treatment of ICH and brain microhemorrhages (BMH). Depending on the results of these studies, Edge may explore the use of its Precisa™ technology to develop a way to administer the drug in a sustained release profile and may also synthesize and test analogs of EZF-0100 to determine the best drug candidate for preclinical development and clinical study in Canada and the US. The project will reinforce ZCADD’s leadership in drug development, attracting new partnerships, investment and revenue generation for the Centre. It will also train next-generation scientists and entrepreneurs and create new jobs for Canadians.

Scale-up of bioaugmentation cultures and development of delivery strategies and monitoring tools for anaerobic benzene and alkylbenzene bioremediation

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Overview

BTEX compounds – benzene, toluene, ethylbenzene and xylenes – are natural components of crude oil and petroleum and are used in the synthesis of a wide range of useful materials and chemicals. They are also toxic, and benzene in particular is a known human carcinogen. As a result of extraction, transportation and refining processes, as well as accidental spills and leaks, BTEX compounds frequently pollute groundwater in all industrialized regions of the globe. In Canada and elsewhere, remediation of contaminated sites is difficult and costly. When possible, affected soils are dug up and treated or disposed of offsite. Dr. Elizabeth Edwards of the University of Toronto is working with SiREM, a Canadian leader in bioremediation, to scale up and commercialize anaerobic bioaugmentation cultures for in situ BTEX remediation. These cultures were developed in Dr. Edwards’ lab where genomic knowledge was used to identify novel benzene-depleting microbial strains. Bioaugmentation, or the injection of specific microbes into contaminated sites, could significantly accelerate the rate of biodegradation, leading to the cleanup of these sites. How well the cultures perform this biodegradation should be understood in 1-3 years, leading to a cost-effective approach for cleanup of BTEX-contaminated sites. If successful, this project would be the first commercial application of bioaugmentation for anaerobic BTEX degradation. It would lead to more widespread cleanup of contaminated sites where currently technologies are not feasible or too expensive. It will enable remediation of soils in-place, as opposed to excavation and removal. There are also significant economic benefits, as the global bioremediation market was conservatively estimated at $1.5 billion in 2009 and is now probably greater than $10 billion and continuing to grow.

A genetic toolbox for tomato flavour differentiation

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Overview

Tomatoes, it is said, are the quintessence of summer in a bite. They are also responsible for more than half a billion dollars in annual farm gate sales and are Canada’s biggest fresh vegetable export. Canadian growers are facing competition due to lower production costs in other regions, leading to difficulties maintaining their market share. Canadian producers need to innovate in order to offer a differentiated product that will give them a competitive edge. Generally, plant breeding programs focus on production traits, such as yield or disease resistance. Vineland Research and Innovation Centre (Vineland) is working with Dr. Charles Goulet of Université Laval to ensure new tomato varieties possess these traits, in addition to something more important to the consumer – flavour. Flavour is a complex trait, reflecting sugar, acid and aroma, as well as texture. Because aroma is defined by more than 30 volatile chemicals and dozens of genes, genomics can greatly facilitate breeding with much greater precision than ever before. This project will use variation in aroma-related genes to develop new tomatoes with differentiated flavour. The resulting plant lines will be used to breed tasty tomatoes at Vineland, and will be made available to other tomato breeders. The first varieties should be commercially available within three years of the project’s completion. The development of locally-adapted, flavourful tomato cultivars will give Canadian greenhouse producers a clear advantage in a competitive consumer market, with total direct economic benefits estimated at more than $30 million per year.

Clinical development and translation of genomics-driven paediatric cancer diagnostics using NanoString

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Overview

Over the past decade, there have been many high-impact, genomics-driven cancer discoveries. The overriding challenge, however, lies in making the transition from the laboratory to the clinic – literally, bench to bedside. Toronto’s SickKids is a leader in the discovery and implementation of clinical diagnostics for children’s health. NanoString Technologies is a leader in providing tools to individual labs to enable laboratory-developed tests. Now, their individual strengths are being brought together to develop additional tools for diagnosing cancer in children that will deliver key information in a targeted, cost-effective and timely way. Led at Sick Kids by Dr. Cynthia Hawkins and Mr. John Racher, in partnership with NanoString Technologies, their initial work will focus on low-grade glioma (brain tumours), leukemia and soft-tissue sarcoma, for which no comprehensive tests currently exist. Further along, the tests can be expanded to adult cancers as well. Within three-to-five years, their work will result in marketable diagnostic tests for pediatric cancer. This will improve survival times and quality of life for children with cancer, reduce healthcare costs and generate licensing revenue, which will be shared between the partners. This is a market with high demand and low competition, underscoring the importance of this product.