Personalized Medicine

Introducing Personalized Medicine

Edward Abrahams

When it comes to medicine, one size does not fit all.

Treatments and prevention strategies that help some are ineffective for others.

We've known this for a long time.

President, Personalized Medicine Coalition

William Osler (1849-1919), a Canadian physician sometimes referred to as the father of modern medicine, once wrote that “variability is the law of life. As no two faces are the same,” he noted, “so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease.”

But until the beginning of the 21st century following the mapping of the human genome, physicians lacked the tools and technologies necessary to understand the reasons for variability among patients. Physicians treated all patients essentially the same, relying on trial and error to find the right solution to a particular patient’s predicament.

Personalized medicine allows us to do much better. Also called precision or individualized medicine, personalized medicine is an evolving field in which physicians use diagnostic tests, often but not always genetic, to determine which medical treatments will work best for each patient. By combining data from diagnostic tests with an individual’s medical history, circumstances, and values, health care providers can develop targeted treatment and prevention plans.

Genetic testing, for example, can help physicians predict how a patient’s body may metabolize certain drugs. Genetically-guided cancer therapies can target the unique set of molecular variables that drive a patient’s particular cancer. And advanced computing techniques that aggregate and compare real-world data can help tailor health care interventions more closely to the wide range of biological and

environmental characteristics that impact human health.

Health systems are still developing and adopting the updated policies and procedures that are necessary to facilitate the widespread implementation of personalized medicine. Change does not come easily. But because biology is complex, it demands that we employ more sophisticated approaches to treating patients.

As we learn more about the root causes of certain diseases and develop new ways of delivering health care to patients at home and in physicians’ offices, proponents of personalized medicine envision a new era of medicine in keeping with Osler’s appreciation of the principle of individual variation. It will be one that promises better outcomes for patients at lower systemic costs because medicine in the future will become more targeted and more efficient.

The national CanPath study is a partnership of seven regional cohorts that, together, span all 10 provinces: the BC Generations Project, Alberta’s Tomorrow Project, Healthy Future Sask, the Manitoba Tomorrow Project, the Ontario Health Study, CARTaGENE (Quebec), and Atlantic PATH.

A unique Canadian resource to enable early disease detection and prevention

One of the most exciting applications of personalized medicine is the potential to identify people at risk of developing a disease years before they're in a doctor’s office needing treatment. As CanPath follows people over decades, some participants who provided a biological sample will develop a disease. Using the samples collected before people develop a disease, scientists can look for genetic and molecular markers that suggest whether someone might be at a greater risk of disease, thereby enabling earlier and more targeted interventions.

Personalized medicine has tremendous potential to improve patient care by tailoring medical interventions to an individual’s unique genetic makeup and life history. Yet, the implementation of personalized medicine programs is challenging as it requires high-quality data collected from a large group of people to capture the complex factors that shape an individual’s health trajectory. In Canada, the promise of personalized medicine is within reach through the Canadian Partnership for Tomorrow’s Health (CanPath).

CanPath collects detailed information from one in every 100 Canadians to learn more about how biology, behaviours, and environmental exposures influence the development of chronic diseases and cancer. Over the past decade, CanPath has collected data and biological samples from more than 330,000

volunteer Canadians, making the study a valuable living population laboratory and the largest health data collection of its kind in the nation’s history.

CanPath, which has been designed to follow participants for five decades, provides a national platform for made-in-Canada health solutions that will benefit Canadians today and in the future. Never before was this more clearly demonstrated than when CanPath data and biological samples enabled researchers to study the factors that affect an individual’s susceptibility and response to COVID-19 infection, as well as the efficacy of vaccines. Understanding how an individual’s genetics, lifestyle, and environment shape vulnerability to disease will only become more pressing in the future with increased population aging and the health threats posed by climate change.

Understanding the health impacts of climate change

Climate change will pose one of the largest threats to our health and our planet in the years to come. With its broad collection of data spanning decades, CanPath offers scientists a chance to understand how different people might be vulnerable to the impacts of a changing environment today and to predict how people will respond to a changing climate in the future. Already, CanPath has enabled Canadian researchers to discover how a collection of environmental factors such as air pollution and neighbourhood walkability, collectively known as our personal exposome, interact with our underlying biology to influence health outcomes. Personalized medicine is a promise for tomorrow that CanPath scientists are delivering on today.

To learn more about how CanPath is building a healthier Canada, visit canpath.ca

Edward Abrahams

Dr. John McLaughlin Executive Director, Canadian Partnership for Tomorrow’s Health

This article was sponsored by the Canadian Partnership for Tomorrow’s Health

Dr. Philip Awadalla National Scientific Director, Canadian Partnership for Tomorrow’s Health

To learn more, visit personalized medicine coalition.org.

Eliminate the Trial and Error Approach in Finding the Right Medication

Pharmacogenetic testing is changing how medications are prescribed and taking away much of the guesswork, especially for mental health and pain medications.

COVID-19 has led to new or exacerbated stress, anxiety, and depression for many.1 As a result, prescriptions for mental health medications have increased and with them, challenges in terms of efficacy and side effects.2

Harnessing the Power of AI to Help Patients Live Longer

Pentavere’s DARWEN™ dramatically accelerates discovery of insights buried in hard-to-access clinical text to help health care providers make better treatment decisions.

Dr. Christine Brezden-Masley says she has seen a revolution in cancer treatment since she began practising in 2004. Researchers can now identify the genetic drivers of certain cancers, allowing health care providers to deliver targeted treatment to a subgroup of patients.

“Non-small cell lung cancer, for example, has specific drivers and now we have drugs to target these drivers,” says Dr. Brezden-Masley, Medical Director of the Cancer Program at Sinai Health in Toronto. “Patients are living years longer with advanced disease.”

These strides in medicine are coming at the same time as advances in artificial intelligence (AI).

Dr. Katherine Siminovitch Genetics Researcher, Rheumatologist, & Co-Founder, Inagene Diagnostics

This is because one size does not fit all. More than 98 percent of us have genetic variants that impact our response to medications, which can explain the trialand-error approach to prescribing, especially with mental health and pain medications.

The transformative science of pharmacogenetics

Dr. Katherine Siminovitch, a genetics researcher and rheumatologist, co-founded Inagene Diagnostics to help accelerate the translation of new genetics knowledge into more effective patient care. “Being able to bring Canadians the transformative science of pharmacogenetics and witness the power of such information to guide, individualize, and optimize medication choices is incredibly rewarding,” she says.

Susan, 3 a nurse from Alberta, knows firsthand how impactful pharmacogenetic testing can be. After cycling through antidepressants for 15 years, an Inagene test demonstrated that all the medications she had been on were in fact not right for her. She’s finally on a “green” medication and was able to return to work and a normal quality of life. “I’m telling family members and colleagues about this incredible test and what it can do to save time and frustration,” she says.

Inagene’s Personalized Insights™ at-home saliva test is processed at its Toronto lab and results are available within seven days of the sample being received.

Health care technology company Pentavere has a breakthrough AI technology engine, DARWEN™, that rapidly extracts, structures, and analyzes complex clinical documentation. This enables health care providers to better understand real-world patients and make treatment decisions based on large and representative patient populations.

“A clinical trial may provide information based on 1,000 patients, while real-world evidence can include a much larger group of patients,” Dr. Brezden-Masley says. “Or, if a clinical trial was performed in another country, we can look at real-world evidence to see how effective the treatment has been in Canada. We have a wealth of digital data and Pentavere allows us to efficiently harness its power.”

For a woman with dense breast tissue, a mammogram may not be the most effective means to test for breast cancer. Yet, for the majority of women a mammogram is the best option. This is a perfect example of the need for personalized options in oncology — and why the Ontario Institute for Cancer Research (OICR) is funding Dr. Martin Yaffe at the Sunnybrook Research Institute. Dr. Yaffe is developing a screening tool that uses image analysis and artificial intelligence to determine which women should receive an alternative screening. The desired result is that more women will get the screening they need to detect breast cancers early and that money will be saved in not doing tests on those who won't benefit.

This is just one example of how Ontario cancer researchers are focusing on projects that look at providing the right type of therapy to the right patient at the right time. While for years the focus in cancer treatment was to remove or shrink a tumour using as much force and toxicity as needed, personalized medicine can provide more precise and tailored therapies that look specifically at the individual case and have fewer side effects as a result.

Improved understanding of cancer at a molecular and cellular level has shown that different individuals, even those with the same type of cancer, have different histological types. In

other words, no two breast cancers — or any other type of cancer — are really the same.

“The future of oncology is going to be developing personalized therapies where you're treating each unique patient as having a unique cancer,” says Dr. Laszlo Radvanyi, the OICR’s President and Scientific Director.

For the OICR, this has meant adapting the organization’s strategic plan to focus on areas that support personalized medicine. The OICR’s Adaptive Oncology theme, which this month announced funding for three new studies, was developed to fund research that anticipates and counters tumour evolution by administering the most appropriate therapies at the right time. It has brought together researchers, like Dr. Yaffe, with expertise in genomics, bioinformatics, machine learning, imaging, robotics, and histopathology, in pursuit of practical ways to characterize the diverse properties of tumours and develop clinical tools to adapt treatment strategies accordingly.

“Then that’s synchronized with our other research streams, in which

we support the development of new cancer therapeutics, clinical trials, and preclinical studies aimed at this earlier cancer space in terms of detection and developing diagnostic biomarker tools for better patient selection for therapies,” explains Dr. Radvanyi.

As the tools used to study tumours become more sensitive, researchers can tell what type of mutations or proteins are developing. This is helpful knowledge in determining ways to target the tumour. “You just can't blindly develop therapeutics,” says Dr. Radvanyi. “You must try to understand the cancer at an earlier stage, then more proactively intervene in a very targeted way, understanding the unique phenotype and genotype of each patient's tumour, and then exploiting the most effective therapies.”

While many of these research projects are in very early stages, the speed of progress has been greatly helped by recent funding and a push for more collaborative work across the province. Working together, Ontario’s world-class researchers are poised to optimize and advance personalized cancer innovations.

This article was sponsored by Inagene Diagnostics

ThisarticlewasmadepossiblewithPentavere.

Abigail Cukier

Dr. Christine Brezden-Masley Medical Director of the Cancer Program, Sinai Health

Krista Lamb

Dr. Laszlo Radvanyi President & Scientific Director, Ontario Institute for Cancer Research

MCI Onehealth: Unlocking the Promise of Personalized Medicine

Dr. Alexander Dobranowski Co-Founder & CEO, MCI Onehealth

Faster and more accurate diagnosis. More effective and more precise therapies and treatments. Earlier disease intervention. Clinical decisions informed by data — the patient’s and the population’s.

Khimji Chief Innovation Officer, MCI Onehealth

The goal of personalized medicine is to enable health care providers to quickly, efficiently, and accurately determine and deliver the most appropriate course of action for an individual patient. The goal of MCI Onehealth is to make that possible, for patients in its high-performance health care network, and, ultimately — through example, collaboration, research, and knowledge sharing — for patients everywhere.

Just a year after its founding, MCI Onehealth is well on its way to fulfilling the promise of personalized medicine, building a fully integrated health care and health-data ecosystem piece-bypiece. Its building blocks include:

Watts President, Khure Health

An integrated clinic and research network with virtual care options

• An innovative health care delivery model

A “personalized intelligence” platform

Decision support tools powered by artificial intelligence

• Partnerships and collaborations

Building Block 1: An integrated clinic and research network with virtual care options

Fully integrated health networks support better coordination of care and optimize the delivery of treatment for individual patients.

MCI Onehealth is Canada's leading integrated clinic network, seeing more than a million patients per year through its 25 primary urgent care clinics and its virtual care platform — MCI Connect.

MCI Onehealth is Canada's leading integrated clinic network, seeing more than a million patients per year through its 25 primary urgent care clinics and its virtual care platform — MCI Connect. Staffed by more than 600 family practice and walk-in medical personnel and over 50 in-house specialists, MCI counts among its patients as those who come to it via more than 500 corporate health customers.

An in-house clinical research organization, a team of data scientists, and an expanding range of AI-powered technologies — including remote and real-time patient monitoring solutions — reinforce the network’s capabilities for delivering personalized health care.

Building Block 2: An innovative health care delivery model

At its flagship clinic, MCI Polyclinic, an integrated care model enhances access, quality, and efficiency of the health services provided to MCI Onehealth patients through the convenience of integrated virtual and centralized in-person care, integrated patient record, and referral systems, as well as improved quality control and responsiveness.

“MCI Polyclinic is centralized physical example of the personalized health care model we’ve strategically built across the MCI ecosystem both digitally and physically. It's our centralized hub for the type of care that patients want and deserve — the highest quality, the most convenient and efficient, with the greatest access to services, ongoing attention to their individual diagnoses and treatments, and more-readily available access to in-house advanced clinical treatment and research opportunities,” says Dr. Alexander Dobranowski, Co-Founder and CEO of MCI Onehealth.

Building

Block 3: A “personalized intelligence” platform

With a 30-year history operating as MCI

The Doctor’s Office, MCI Onehealth currently stewards more than 2.5 million patient records. An underlying objective of building this high-performance health care network is to enable an end-to-end personalized patient journey that also captures a more holistic and accurate 360 degree view of the patient’s profile. MCI has built a platform that securely collects and integrates high-quality personal health data essential to personalized health care — from medical records to real-world evidence, whole genome analysis to information captured by wearable technology. MCI refers to this as “personalized intelligence” as in “intel,” information from which you can identify — even predict, and thus prevent — major health concerns such as risk of chronic disease or complications.

“The MCI Onehealth model of care provides personalized care pathways for patients today, and personalized intelligence for their future care,” says Saleema Khimji, Chief Innovation Officer at MCI Onehealth. “With integrated systems and data-driven tools, we believe we can further unlock meaningful insights from consistent and high-quality structured clinical information. As we generate insights through research, we can provide a data-driven, deeply personalized patient profile, accurate and faster diagnosis, and expanded treatment options. Also, by building a richer and deeper patient profile, MCI is simultaneously leveraging this directly into research initiatives and clinical trials, which is a key factor in advancing personalized medicine.”

Building Block 4: Decision support tools powered by artificial intelligence

Through the use of clinical data, machine learning and artificial intelligence, MCI Onehealth’s Khure Health tool is enabling primary care physicians to rapidly screen and identify patients with rare diseases and chronic diseases, bringing average diagnosis time down and facilitating more personalized treatment including clinical trial recruitment.

“Linking Khure’s functional clinical intelligence platform to our existing databases is an integral step in redefining the way that technology is used in MCI’s health care network. Identifying undiagnosed patients with rare diseases empowers primary care doctors with the essential tools and technology to take meaningful steps forward towards a future of preventive care,” says Don Watts, President of Khure Health, an MCI Onehealth subsidiary. “This is also a very exciting time with Khure recently launching its new clinical trial offering that utilizes its AI-enabled clinical intelligence platform to accelerate patient recruitment for clinical trials and speed scientific discovery. This platform will

help bring much needed new precision medicines and clinical knowledge to benefit patients in need faster than ever before.”

Integrating multiple tools like this into an easy-to-use interface to support physicians during the delivery of care is an important outcome of MCI Onehealth’s personalized medicine vision.

Building Block 5: Fostering innovative partnerships and collaborations

Data sharing and collaboration are crucial for advancing personalized medicine and being able to extend its benefits across health systems. MCI Onehealth is collecting and linking higher-quality data points from more diverse sources, and structuring it to share with the key stakeholders that require such data to advance personalized medicine research, technologies, treatments, and therapies.

Data sharing and collaboration are crucial for advancing personalized medicine and being able to extend its benefits across health systems.

The precision-medicine ecosystem has provided new ways in which health care providers, patients, research enterprises, health information technology players, and other industries are intersecting, interacting, learning, and collaborating. These “feedback loops” ensure that what is learned from research can quickly be adopted in practice, benefiting patients sooner, with insights that are relevant to their individual health.

MCI Onehealth is developing realworld, evidence-based approaches to collaboration and creating unique feedback loops with the pharmaceutical and life science sector and world-class academic and research institutions. These efforts will create a foundation for a continuously learning health care system model and, eventually, one in which the feedback loops between the various information centers will be shared in real-time.

MCI Onehealth is collaborating with the Stanford Healthcare Innovation Lab as a founding member of its Affiliates Program, a newly established health care collaboration centered around innovation in health care and personalized medicine. With Stanford, MCI Onehealth is also participating in a COVID-19 wearables study, and will embark on co-authoring research publications and exploring further research studies related to chronic diseases, mental health, genomics, and multi-omics.

At MCI Onehealth, the pieces are coming together to deliver on the enormous potential of personalized medicine to give better clinical outcomes, improve access to care, make it higher quality, and ultimately — through earlier intervention in disease and preventative care — reduce health system and societal costs. For MCI Onehealth patients, health care providers, and leadership — it’s personal.

To learn more, visit mcione health.com

The future of medicine will be personal.

MCI Onehealth

PHOTO COURTESY OF MCI ONEHEALTH

Saleema

Don

Did You Know That DNA Testing Can Improve Your Health?

The concept of bio-individuality has taken off in the world of nutrition. The idea is that there's no one-size-fits-all approach to health, and that we're all unique in our biological makeup and requirements. A lot of bio-individuality has to do with genomics — our personal DNA. This concept goes beyond nutrition, and it’s now being applied to medicine, too, thanks to the science of pharmacogenomics.

“Pharmacogenomics is the study of how DNA relates to medication response,” says Sandra Hanna, a pharmacist at Personalized Prescribing Inc., a consumer pharmacogenomic testing company. By testing and analyzing patients’ DNA, the organization helps determine which medication would work best for people based on their unique genetic makeup.

Going beyond traditional mental illness medication prescribing “At Personalized Prescribing Inc., we focus on how people’s genetics or DNA relates to anti-depressant response in particular,” says Hanna.

If a doctor diagnoses someone with depression or anxiety, a selective serotonin reuptake inhibitor (SSRI) is generally the first-line treatment. However, there are many first-line SSRIs and patients’ responses to SSRIs vary widely. Part of the reason for this is due to their unique genetic makeup. Genetic factors influence how our bodies respond to drugs, and this includes differences in how we metabolize them.

“The majority of anti-depressant medications are cleared predominantly by two different liver enzymes, so we test those enzymes,” explains Hanna. “Some people have poor

clearance, so they accumulate the medication in their bloodstream. For these patients, we may recommend a dose reduction. Other people are ultra-rapid metabolizers, so they clear the medication so fast that it doesn’t reach the brain in sufficient enough concentrations to be effective. We may recommend an alternative drug for these patients.” These recommendations are evidence based, and backed by the FDA or other relevant guideline.

Personalized recommendations and prescriptions

Metabolism is well-studied and understood, but Personalized Prescribing Inc. takes things a step further by testing pharmacodynamic genes — in this case, brain receptor genes. “We test the capacity for an anti-depressant medication to actually enter the brain via the blood-brain barrier,” says Hanna. “We also test the different genetic expression of the relevant serotonin or dopamine receptor genes to see if they can effectively be blocked or agonized as necessary in order to create the desired therapeutic response.”

Combining DNA testing with the personalized analysis and evidence-based recommendations from its team of in-house pharmacists, Personalized Prescribing Inc. is helping to take the guesswork out of prescribing. By helping doctors and patients to identify the optimal medication or dosage, it’s delivering the next frontier of medicine — personalized and tailored medicine, which increases the efficacy of medications and reduces negative side effects.

“I see this being a mainstay in health care in the future because it improves patients’ quality of life, it saves lives, and it saves everyone money,” says Hanna.

I see this being a mainstay in health care in the future because it improves patients’ quality of life, it saves lives, and it saves everyone money.

Tania Amardeil

Sandra Hanna Pharmacist, Personalized Prescribing Inc.

Building Canada’s Life Sciences Industry for the Post-Pandemic Era

COVID-19 spotlighted the need for a strong domestic life sciences industry — both to address and secure the health of Canadians, and drive economic recovery and growth. Governments and other stakeholders are stepping up in historic ways to seize the moment.

For example, the federal government recognized this indispensability with $2.2 billion committed to the life sciences sector in Budget 2021. In addition to increasing public sector support, we have also seen unprecedented private investment — with billions of dollars of venture capital going into Canadian life sciences companies since the pandemic began.

It's a compelling moment to be part of this ecosystem, and with a wealth of scientific discovery, Canada is primed to be a global leader in life sciences. However, to maximize our future successes in the post-pandemic era, we need to double down. Doing so means addressing three pressing problems and focusing all of our energies on three key outcomes:

1. We need more domestic venture capital.

Of the billions invested into life sciences by venture capital (VC) funders last year, only 10 percent were from Canadian investors. The good news is that life sciences-focused VC funds in Canada continue to strengthen; with about $1.3 billion raised last year. We also saw a number of the largest fund closings ever. However, foreign limited partners (LPs) comprise the majority of LPs in Canadian VC funds. We certainly welcome foreign direct investment,

but to collaborate with those investors, and build a sustainable Canadian ecosystem with them, we must keep building Canadian VCs, too.

2. We need more commerciallyfocused wet-lab space. This issue is a fundamental roadblock in Toronto, Vancouver, and Montreal. At adMare BioInnovations, we have two multi-tenant Innovation Centres — a 40,000 square foot facility in Vancouver and a 150,000 square foot site in Montreal, where we recently completed a major expansion, essentially doubling the rentable space. With approximately 35 companies residing with us, these Innovation Centres are at capacity. And given the market demand we've seen, we could likely fill them twice over.

3. We need more domestic talent. The greatest competitive advantage of our life sciences industry is people. It's estimated however, that 65,000 additional workers will be needed to support the bioeconomy by the year 2029. The enormous growth that the existing industry is driving has created a “sweet headache,” a problem of success, a skills gap that we need to address now.

The pressing issues brought on by the pandemic have caused our adMare BioInnovations team to think about how we seize this opportunity to focus on three specific areas: building investable companies, robust ecosystems, and industry-ready talent — and then re-investing our returns back into the Canadian industry to ensure it's sustained for the long-term.

1. We build companies by partnering with and investing in technology innovators and entrepreneurs — namely academic researchers and emerging Canadian life sciences companies — and bringing our scientific and commercial expertise, specialized R&D infrastructure, and investment capital to the table.

2. We build ecosystems based around physical infrastructure such as our Innovation Centres, which support the growth of Canadian life sciences companies and the development of Canadian innovations by providing move-in-ready lab and office space with shared services and amenities. We also help build the national ecosystem by bringing together and supporting key organizations, as well as producing high-value industry events; and by building connectivity through the adMare Community digital platform.

3. We build talent by training the highly-qualified personnel — from undergrads to industry executives — who will drive the growth of the industry. The adMare Academy provides four distinct program streams: the Executive Institute, the BioInnovation Scientist Program, the Fellowship Program, and the Undergraduate Institute. It has also recently partnered with the Canadian Alliance for Skills and Training in Life Sciences (CASTL) to deliver world-class technical training for Canada’s biopharmaceutical manufacturing sector.

We know what happens when we focus on the interconnected processes of building companies, building ecosystems, and building talent — the results and the data are overwhelmingly clear. We know that this approach works because our 25 portfolio companies have attracted more than $1.4 billion of real risk capital, have a combined value of over $3 billion, and employ almost 1,000 Canadians, and the adMare Academy has trained 500 alumni, 95 perecent of whom are now working to build our life sciences industry.

Even so, no one team alone is going to make our industry a global leader. If we all focus together on these three things — building companies, building ecosystems, and building talent — we will realize our shared vision of Canadian life sciences leading the world.

To learn more about how adMare may be of value to you, connect with our team by visiting us at admarebio.com or contacting us at info@admare bio.com

This article was sponsored by adMare Bioinnovations