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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.

Standardization of molecular diagnostic testing for non-small cell lung cancer

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Overview

Non-small cell lung cancer is the most common type of lung cancer, accounting for 85 per cent of cases. Specific genetic mutations in a patient’s tumour can determine which drug will work best for that patient. As new targetable genetic mutations become known, it is more important than ever to be able to carry out genetic analysis of patient samples. Dr. David Stewart, from The Ottawa Hospital and the University of Ottawa, is working with the Eastern Ontario Regional Laboratory Association (EORLA) to develop an assay that can accurately detect important genetic mutations in the very small biopsy samples that can be obtained safely from most patients with advanced lung cancer. The assays will test for multiple genetic variations at once, for a more timely result than is possible with current sequential testing strategies. Patients will benefit from the rapid availability of information that will permit them to receive the most appropriate treatment. The financial benefits are also significant. If this new assay is implemented across the country, it could result in savings of $35.9 million in testing costs and $151.4 million overall due to the elimination of ineffective treatments. The project team will assemble a national advisory board to drive national translation of its technology so that these savings can be realized.

Application of genomic selection in turkeys for health, welfare, efficiency and production traits

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Overview

Dr. Christine Baes of the University of Guelph and Ben Wood of Hybrid Turkeys will be collaborating to adapt and apply genomic tools developed in other livestock species to improve the health, welfare and productivity of Canadian turkeys. Hybrid Turkeys’ parent company, Hendrix Genetics, has already implemented genomic selection in layer chickens and pigs and it will now adapt and apply the technology to achieve improvements in feed efficiency, bodyweight, yield, egg production and livability in commercial turkeys. This will lead to estimated economic gains for the Canadian turkey industry of $39 million over the next five years. The project will also have environmental benefits due to improved feed efficiency and reduced manure and greenhouse gas production. Hybrid Turkeys is part of Hendrix Genetics, a multi-species breeding company with primary activities in layers, turkeys, pigs, aquaculture, and traditional poultry. Its R&D headquarters is located in Kitchener, Ontario. By applying advanced genomic selection, Canada’s role as a supplier of turkey genetics to the world will be secured. By more accurately estimating the genetic potential of selection candidates, the rate of genetic gain can be increased from 15 per cent to 60 per cent, depending on the trait chosen. These improvements will provide value across the production chain, from breeders and farmers to turkey processors and, ultimately, to consumers.

Translating OMICS for competitive dairy products

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Overview

Aged cheddar is a classic of cheese boards, pairing with everything from apple pie to zinfandel. Parmalat Canada is the number one producer of premium-quality aged cheddar that has been winning many cheese contests including the 2016 world cheese championship. Demand for aged cheddar is projected to steadily increase in the future, requiring Parmalat to increase its manufacturing capacity. Trade deals (such as CETA) make it more urgent for Parmalat Canada to gain efficiency and protect its market share. To achieve this goal, Parmalat Canada is working with Dr. Gisele LaPointe of the University of Guelph, a well-known scientist in the field, to validate and implement metagenomic, metaproteomic and metabolomics tools modified to meet the technical requirements of cheese production. The project will improve manufacturing processes and controls to overcome current bottlenecks and significantly increase the production capacity of high-quality, competitive aged cheddar cheese. With over 120 years of brand heritage in the Canadian dairy industry, Parmalat Canada is committed to the health and wellness of Canadians and markets a variety of high-quality food products that help them keep balance in their lives. Parmalat Canada produces milk and dairy products, fruit juices, cultured products, cheese products and table spreads, employing more than 3,000 people, with 16 operating facilities across the country. This project will bring the Canadian knowledge base related to cheese making processes into a new era. With increased production of high quality cheese, Parmalat will contribute even more to the Canadian economy. At the same time, our dairy farmers will benefit significantly from the increased demand for and utilization of Canadian milk and increased revenues for dairy farmers of about $28 million a year.

Increasing Yield in Canola Using Genomic Solutions

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Overview

The world’s population is growing and so is demand for the crops to feed it, among them canola. The canola industry in Canada accounts for nearly a third of the gross production value of all Canadian crops, generating $19.3 billion and nearly 250,000 jobs across Canada. The industry has set a goal of increasing yield by 53 per cent in the next 10 years. Traditional breeding techniques are not sufficient to meet this goal; new technologies are needed. Dr. Peter Pauls and collaborators at the University of Guelph have identified the genetic links of traits that can be incorporated into canola. The new traits are expected to significantly enhance crop productivity by increasing photosynthetic capacity, without negatively impacting seed quality. The researchers are working with Benson Hill Biosystems (BHB), an innovative crop genetics firm, combining their strengths to produce game-changing varieties of canola for producers across Canada. The results of this project will enable commercialization of the improved plants through licensing or collaborative development agreements. Increasing the yield of the canola crop benefits growers and others across the value chain, growing industry revenues by $3-$4 billion per year. BHB will also establish a Canadian subsidiary, CanolaCo, for this project that will result in newly created jobs for Canadians.