Improving patient matching to therapy (PMATCH): streamlining clinical trial criteria to guide precision oncology

Overview

Clinical trials are a crucial element of the modern health system. Cancer patients in Canada, however, face substantial barriers to accessing state-of-the-art precision therapies. This is because matching patients to trials is an increasingly resource-intensive and time-consuming task. The disjointed nature of the digital infrastructure means that already overworked clinicians have to spend time parsing through complex eligibility criteria and clinical diagnostic data.

The result is fewer patients are enrolled in trials for which they are eligible. This project will develop PMATCH, an innovative open-source software platform using powerful machine learning techniques to search through complex clinical and genomic eligibility criteria along with the data generated by each patient during their cancer journey, e.g., blood tests, surgery, family history.

Clinicians will be able to match their patients with the best clinical trials for each individual in near-real-time. PMATCH will also standardize the clinical and sequencing data and ensure their FAIRness (findability, accessibility, interoperability and reusability).

Expected benefits of the PMATCH pilot include a 50 per cent increase in patients matched to precision medicine trials across Ontario, acceleration of the identification of actionable biomarkers, increased pharmaceutical support for academic clinical trials, and improved patient experience in trials.

EpiSign International: Health system impact assessment and expanding clinical utilization of epi/genomic testing in rare diseases and beyond

Overview

An estimated 1 in 15 children is born with a rare genetic disease. Since 75 per cent of the 4,000 diseases manifest in childhood, children affected by them occupy 25 per cent of pediatric hospital beds in Canada, with diagnostic assessments often exceeding $10,000 per child. Despite advances in genome sequencing, most people with rare disorders remain undiagnosed, resulting in a significant socioeconomic burden related to the so-called “diagnostic odyssey”, impacting treatment, reproductive planning and access to specialized care services. In addition to genetics, a significant cause of birth and neurodevelopmental defects involves prenatal exposures to teratogenic toxins including lifestyle choices, drugs and pathogens.

Toxic exposures are challenging to resolve due to the lack of genetic biomarkers that can be detected with standard molecular tests. In partnership with Canadian biotech start-up EpiSign Inc., London Health Sciences Centre’s Dr. Bekim Sadikovic has developed the first technology, called EpiSign, that uses a patient’s epigenome to diagnose both genetic and teratogenic disorders.

EpiSign’s proprietary and continuously evolving AI-based algorithms compare Illumina microarray-generated epigenetic DNA methylation profiles in a patient’s blood to the EpiSign Knowledge Database, the largest, rare disorder DNA methylation database.

This project will expand clinical adoption of EpiSign as a Tier I test, using new Illumina technology. The project will advance molecular diagnostics of rare disorders and enhance Canada’s leadership in clinical epigenomics. Improved and earlier diagnosis will give patients better access to care options and support networks, while improving health equity and socioeconomic impacts on healthcare systems in Canada and internationally.

Genomic Applications Partnership Program (GAPP)

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The Genomic Applications Partnership Program (GAPP) funds downstream research and development (R&D) projects that address real-world opportunities and challenges defined by “Receptor” organizations such as industry, government, or not-for-profit entities. These organizations should have the expertise, resources and commitment to commercialize or implement the project’s outcomes. Projects must be active collaborations between the Receptor organization (Canadian or international) and a Canadian academic researcher. Both must play an integral role in the project. These projects are co-funded by Receptors and other stakeholders and must have the potential to generate significant social and/or economic benefits for Canada. The GAPP aims to:

  • Accelerate the application of Canadian genomics-derived solutions from academia to real-world opportunities and challenges defined by industry, not-for-profit and public-sector Receptors.
  • Channel Canada’s genomics capacity into sustainable innovations that benefit Canadians.
  • Enhance the value of Canadian genomics technologies by de-risking and incentivizing follow-on investment from industry and other partners.
  • Foster mutually beneficial collaboration and knowledge exchange between Canadian academia and technology receptors.

GAPP is open to projects across all sectors. For examples of previously funded projects, see Funded GAPP Projects

Key Parameters of the Program:

  • Total project size: $300,000 to $6 million.
  • Co-Funding: Up to 1/3 investment from Genome Canada; Receptor co-funding (cash and/or in-kind) that is equal to or greater than Genome Canada’s contribution; and any remaining co-funding from other eligible sources. For more information, see Section 4 and Appendix 2 of the GAPP Investment Strategy and Guidelines.
  • Project term: 2 – 3 years. Shorter or longer terms will be considered only if strong rationale is provided.
  • Project stage: Small-scale proof-of-concept / pilot projects through to large-scale projects will be accepted. Projects should not be in discovery phase.

Project Eligibility:

To be eligible for the GAPP, a project must:

  • Develop and apply a genomics-derived or genomics-enabling tool, product or process to an opportunity or challenge defined by the Receptor(s);
  • Focus on late stage R&D that will position the innovation for near-term implementation/commercialization;
  • Be co-led by an academic and a Receptor organization in partnership, with active and necessary roles for both; and
  • Demonstrate the potential to generate significant social and/or economic benefits for Canada.

Receptor Definition

A Receptor is defined as an organization that intends to put the resulting innovation into practice (in internal operations, by commercialization, or otherwise making it available to its ultimate users). Eligible Receptors include:

  • Companies (private / public, Canadian / foreign-owned);
  • Industry consortia;
  • Government departments and agencies (federal, provincial and municipal);
  • Healthcare organizations; and
  • Not-for-profit organizations

Small or start-up companies may be considered, as per the Investment Strategy Guidelines.

Application Process:

There is a three-stage, gated application process for this program:

  • Expression of Interest (EOI)
  • Project Pitch
  • Supplementary Proposal

Note that the EOI and Project Pitch content resembles a business case for the proposed project. At each of the above stages, Ontario Genomics has developed a review process, where a panel of industry experts and entrepreneurs provide feedback to help teams navigate the application and increase their competitiveness. These reviews are mandatory for all Ontario projects. Applicants should anticipate the following phases in the application process:

  • Register your intent to apply to Ontario Genomics and obtain EOI form.
  • Complete a draft EOI and submit to Ontario Genomics.
  • Present a face-to-face business pitch to Ontario Genomics’ GAPP Review Panel.
  • Develop the final EOI through active collaboration with Ontario Genomics.
  • Submit EOI to Genome Canada via Ontario Genomics.
  • For teams invited to Project Pitch stage:
    • Present practice pitch to Ontario Genomics before official pitch to Genome Canada.
  • For teams invited to Supplementary Proposal stage:
    • Submit draft applications to Ontario Genomics for panel review before submission to Genome Canada.

Genomic Applications Partnership Program (GAPP)

The Genomic Applications Partnership Program (GAPP) funds translational research and development projects that address real-world challenges and opportunities as identified by industry, government, not-for-profits, and other “receptors” of genomics knowledge and technology. Launched on June 03, 2013, Genome Canada’s GAPP program aims to fund projects that have a clear and defined partnership between Academia and User partners (receptors) to promote the application of genomics-derived solutions that address key sector challenges or opportunities and which will have socioeconomic benefit to Canada.

Funded Ontario GAPP Projects

On March 9, 2022, The Honourable François-Philippe Champagne, Minister of Innovation, Science and Industry, announced federal support through Genome Canada to five Ontario Genomics-led and co-led research and development projects as part of the Genomic Applications Partnership Program (GAPP), that will mobilize genomics out of the lab and deliver real-world benefits.

SALMON and CHIPS – Commercial application of genomics to maximize genetic improvement of farmed Atlantic salmon on the East coast of Canada

Overview

Aquaculture companies are increasingly incorporating genomics technology into their breeding programs to develop desirable stock traits for improved growth and disease resistance. To retain its ability to compete internationally, Cooke Aquaculture/Kelly Cove Salmon will partner with Dr. Elizabeth Boulding and her academic group from the University of Guelph to incorporate genomics marker technology into Kelly Cove Salmon’s current breeding program. This will allow the company to improve the effectiveness of its breeding program and increase the resistance of its salmon to diseases and parasites. The company aims to implement an advanced genomics technology known as SNP-chips, which when blended with conventional animal breeding techniques, can yield significant increases in the survival rates of eggs and juvenile stages, as well as improved saltwater performance. The implementation of this genomics technology is expected to increase the quality and sales of Kelly Cove’s salmon, and improve profitability by reducing expenditures on vaccines and medication. Strengthening Kelly Cove Salmon and its parent company, Cooke Aquaculture, will be good news for the more than 1,700 current employees in Atlantic Canada, and will lead to increased employment in rural and coastal communities.

Genomics for a competitive greenhouse vegetable industry

Overview

Tomatoes, peppers and cucumbers generate more than $1 billion in annual sales for the Canadian greenhouse vegetable industry. These plants are susceptible to a number of diseases, which threaten crops and decrease profits for producers. In order to maintain a competitive edge, create growth and ensure future success, Canada’s greenhouse vegetable industry needs plant varieties that are resistant to disease. To address this challenge, Vineland Research and Innovation Centre will partner with Dr. Keiko Yoshioka, a leading academic from the University of Toronto, who has discovered a key gene involved in plant disease resistance. By using proven gene technologies to enhance disease resistance in greenhouse vegetables, this project aims to develop new commercial traits and varieties for Canada’s vegetable industry. These technologies will benefit Canada’s greenhouse vegetable industry by adding value to Canadian greenhouse vegetables, and fostering economic growth, increased exports, reducing competition from imports.

Development of low cost diagnostic platform for infectious disease testing

Overview

Conventional lab testing for infectious diseases such as Hepatitis C, malaria and tuberculosis is inefficient and not cost-effective, particularly in developing countries. The development of fast and accurate point-of-care testing for these infections would significantly improve the clinical management of infectious diseases. For this research, Xagenic will partner with Dr. Shana Kelley, a leading academic from the University of Toronto, to leverage expertise in viral assay development, sensor technology and plastic chip fabrication. This project will lead to a single affordable and accurate genotyping test to screen for infectious pathogens, and will provide a new solution for rapid disease diagnosis. The low-cost, disposable, battery-powered testing device will identify pathogens in human blood in minutes, which could reduce infectious disease in Canada and around the world, and dramatically improve disease management. The launch of this new product line by Xagenic will result in increased revenues and significant job creation within the company.

Cardiovascular Biomarker Translation (CBT) program

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

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

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.