Pursuing cures and advancing innovation | 080

Biotechnology Focus Podcast

080 | Pursuing cures and advancing innovation

Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what’s been happening on Canada’s biotech scene. It has been a busy last couple of weeks as the new genomics cloud platform was launched, a researcher from Roche Canada shares her input on future of innovation in cancer care, and the fight against cancer innovation trust invests almost half a mil in Ontario research technologies.

+++++

The world is opening up to the idea of genome sequencing. What was once a far-fetched idea is now beginning to materialize – and we are only at the tip of the iceberg. Information technology like Facebook, Google, Wikipedia and Uber are all prime examples of impactful software platforms that connect people with data that have set the stage for the next act.

When you look at where DNA sequencing began back in the 1970’s with the “Sanger sequencing method” as a process of determining the order of bases in the length of DNA, we’ve come a long way. But still, researchers are at the forefront of this revolution of gathering our personalized genetic information and using it to power the next generation of safer and more effective “precision” medicines.

This is where Marc Fiume and his team from DNAstack, a Toronto-based cloud genomics company, have their role to play. Started in 2014, the company began work with some exciting researchers from around Canada whose hot topics included autism and cancer research. But constantly they were told that the researchers just didn’t have enough samples to make sense of all the data they were collecting and that they really needed a platform that would connect them with other researchers globally who found themselves in the same position. Inspired by the concept of Facebook, they decided to build their own platform where genetic research could transpire among researchers worldwide.

He refers to the lack of data access as “potentially keeping life-saving information in a basement server room” and is one of his biggest frustrations when it comes to genomic research. Unveiling the sequence of a genome is challenging, time-consuming and expensive. Perhaps that is the reason why such a platform can no longer be just a notion, but become a mandatory tool so we can further our knowledge unified, instead of trying to connect the dots apart.

Genome sequencing is a lot like “decoding” of a foreign script or ciphering out a code of each individual’s personal genome. It is a long string of letters that forms a sort of molecular blueprint that is unique for each of us. These “strings” of letters are about six billion long, and currently, researchers are only grasping about a very small per cent of what those letters represent. This is why the need for sharing information should be a necessity.

In an attempt to break this societal self-inflicted mold, Marc worked with Dr. Stephen Scherer from The Centre of Applied Genomics on the “Personal Genome Project Canada” to facilitate the publication of health and genome records online for free. The intention being that whether you are sick or healthy, it is incredibly useful personally and for the research community to have your genome sequenced. Perhaps you have a predisposition to a potentially harmful genetic disease that you were not aware of before and could catch it before it starts, or if you are a carrier, or if you simply want to learn more about your ancestry. All of this is possible with genome sequencing. While some may not be ready to have theirs published online, it could still be made available to you in the privacy of your own home.

Marc and Ryan Cook, the other co-founder of DNAstack, have both tried to decrease the unease attached to publicly airing one’s genome sequence by publishing their own.?“It’s about empowering and making key decisions about their healthcare in a way that’s not scary and also to break down barriers about data sharing,” comments Marc.

There are now 56 genome researchers that are bearing it all for the world to see, and encouragingly are following up on some of the data that they have found.

DNAstack recently launched their Canadian Genomics Cloud platform that is designed to better connect data, researchers and systems across the country to accelerate genomic discoveries and the implementation of precision medicine. It was invented by Canadian leaders with decades of experience in genomics, sequencing, cloud computing, software, security, and policy to democratize access to best-in-class infrastructure while respecting the unique national and provincial requirements for data privacy and security. Their aim is to service the needs of Canadian genome scientists from research institutions, clinical laboratories, pharmaceutical companies, hospitals, and industry.

The hope is to demonstrate that Canada now does have the capacity to do a precision medicine initiative at scale. Canada is really ready for this.” – says Marc.

+++++

For most of us, the start of a new year is a natural time to reflect on our progress as individuals. We take stock of the lives we’ve lived, the advances we’ve made, the impact we’ve had on those around us and the steps we need to take in the year ahead to achieve our goals.?

For the Pharmaceutical and Biotechnology industry, the start of the new year is much the same. Standing at the doorstep of 2018, many of us who have spent our lives trying to advance healthcare around the globe believe that we are at a point in our careers, where science is progressing at a rapid rate.

In fact, some of us would venture that science is progressing at a rate that is outpacing our ability – as healthcare providers, as governments, as payers and as hospital institutions – to integrate these cutting-edge advances into clinical practice. While this reality poses significant challenges, it’s exciting to be on the threshold of so many unprecedented discoveries and novel treatment approaches for some of the world’s most devastating diseases.

The field of biotechnology is rich with discoveries that will have a dramatic impact on Canadians in 2018 and beyond. However, there are three key developments in the area of oncology in which we can expect to see some of the most transformative and immediate changes. These include:

the expanded role of diagnostics to optimize treatment choice;

the adoption of histology-agnostic treatment approaches; and

the next phase of true precision medicine

?

Expanded Role of Diagnostics

In recent years, the use of diagnostic tests within the Canadian cancer care setting has become an increasingly important practice, particularly for guiding treatment decisions and optimizing the patient’s chances for positive outcomes. In fact, it’s estimated that nearly 70 per cent of all treatment decisions today involve a pathology and/or laboratory investigation.

While the role of predictive biomarker testing has already been well established for some time in certain tumour types (such as HER2 in breast cancer or EGFR and ALK in lung cancer) we are witnessing the emergence of two trends that could further enhance patients’ care and their experience with our healthcare system. These include the ability to simultaneously look beyond a single biomarker through genomic profiling, and the viability of liquid/blood-based biomarker testing.

In 2018 we can expect to see a continued shift among healthcare providers to rely more on comprehensive genomic profiling to map each patient’s unique genomic profile to identify alterations across hundreds of genes known to be relevant in the development and progression of cancer. This broad approach optimizes the use of the available tumour tissue and provides physicians with the most comprehensive information to help guide their treatment selection. There is particular value in this approach for patients who have exhausted all standard treatment options or for those with rare forms of cancer with limited known effective treatment options.

Canadian institutions, like the British Columbia Cancer Agency, University Health Network in Toronto and The Jewish General Hospital in Montreal among many others, have already begun to demonstrate international leadership in this area with their in-house testing platforms and world-class genomic research programs. ?We are also seeing the emergence of third-party molecular information providers, such as Foundation Medicine Inc., an organization that has partnered with Roche to offer genomic tests to provide physicians with information about a tumour’s unique genomic profile based on an interrogation of over 300 genes. These external services provide options for institutions that may not have the internal capabilities to offer such testing services and for patients who are looking for more comprehensive diagnostic information. All of these efforts are striving to rapidly expand treatment options by matching patients with approved targeted therapies, immunotherapies, and clinical trials based on their tumour’s molecular profile.

The second emerging trend in the space of predictive biomarkers is blood-based testing, which offers physicians a less-invasive testing mechanism for cases, in which there is insufficient tissue available for analysis. This may also prove to be a better option when a traditional tissue biopsy is not feasible due to tumour location, when a patient is in poor health, or when a physician and/or patient simply prefer a non-surgical option. In addition to supporting initial treatment choice, blood-based testing may also offer physicians the potential for continued monitoring in the future, resulting in earlier detection of disease progression and an assessment of resistance mutations to inform subsequent lines of therapy.

?

A Change in Mindset

Further to the evolution of diagnostic technologies, the increasing prevalence of targeted medicines is fundamentally challenging the way cancer research is conducted. ?We are no longer seeing only large randomized Phase III studies measuring overall survival for drug development, but more novel trial designs, including basket and umbrella studies, as well as smaller Phase II designs to measure the safety and efficacy of a drug. ?These new study approaches are aimed to accelerate scientific advancement and are addressing the challenges that exist when the prevalence of a particular molecular alteration is so limited that traditional trials seeking a large bolus of patients simply aren’t feasible.

In a basket trial, the impact of a single treatment across a spectrum of tumour types harbouring a particular alteration can be investigated. In contrast, umbrella trials inverse the approach, where multiple treatments are studied in patients with a common tumour type but who are stratified by molecular subtype.

Close to home, the Canadian Profiling and Targeted Agent Utilization (CAPTUR) trial sponsored by the Canadian Clinical Trials Group in partnership with several pharmaceutical companies and academic institutions across the country is a combined basket/umbrella study enrolling patients of all cancer types who are stratified into different arms of the study to receive treatments based on the genomic profile of their tumours. ?Studies like CAPTUR will fundamentally shift how physicians view cancer, forcing them to look less at the type of cancer (e.g., breast, lung, colorectal) and focus on the molecular structure of the tumour.

This histology-agnostic approach is one that is also gaining traction with regulatory authorities around the globe. In fact, the U.S. Food and Drug Administration (FDA) recently approved a PD-1 inhibitor to treat patients with any cancer type, provided their tumours were unresectable or metastatic and classified as microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR).? This approval represented a significant departure from the traditional evidence requirements expected from a regulatory body and opens the door for further discussions and opportunities in other countries.

The final development, which seems like a natural extension of our evolving mindset around the use of diagnostics and targeted medicines in oncology is our view regarding how medicines can be engineered to offer truly?individualized treatments to patients.

Though personalized medicines and immunotherapies are no longer considered ‘new’ in the rapidly evolving clinical landscape, the emergence of two types of truly bespoke cancer therapies marry these concepts to create what many consider a bold step in our quest to cure cancer.

Recently, two chimeric antigen receptor (CAR) T-cell therapies were approved in the United States, ushering in the next wave of personalized cancer care. These therapies involve the genetic engineering and reinfusion of a patient’s own T-cells to fight their unique cancers. ?While approved in specific hematologic cancers today, researchers are also exploring these therapies in many solid tumours and the hope remains that they will offer a whole new way to think of treatment in cancer.

Still in its infancy, the second area of significant research is personalized cancer vaccines developed and manufactured for an individual patient based on the molecular profile of their tumours. Where off-the-shelf cancer vaccines have failed in the past, there is hope that these custom, uniquely tailored vaccines, in combination with checkpoint inhibitor therapies will succeed in transforming cancer care. Close

In closing, while it’s easy to become discouraged by the often necessary hurdles required to integrate transformative products into current clinical practice, there has never been a more exciting time for those of who have built a career in the biotechnology industry; and there has never been a more exciting time for those of who have waited for a cure to cancer – a disease that has ravaged many of our families and has taken many of our friends and loved ones.

The reality is that science will continue to outpace clinical practice. But the promise of these discoveries can be realized if we – as stakeholders within the healthcare system – are willing and open-minded to collaborate on solutions, especially as we look at the impact personalized medicines can have in therapeutic areas beyond oncology, offering meaningful solutions to an infinitely greater number of patients, enabling them to live longer, healthier lives.

+++++

The fight against cancer innovation trust announces?four new recipients of funding through its prospects oncology investment competition. Those recipients are Dalriada Therapeutics Inc., 16-Bit Inc., a cancer biomarker study at the Ontario Institute for Cancer Research (OICR), and a virus-based therapeutic under development at the Ottawa Hospital and the?University of Ottawa. ?FACIT’s investments are imperative in bridging the capital gap often experienced by early-stage?Ontario?companies, helping corporations establish jobs and build roots in the province. The wide-ranging scope of the innovations, which span therapeutics, machine learning and biomarker development, reflect the rich talent pool within the?Ontario?oncology research community.

Dalriada?is a Canadian start-up?founded?with a mission to develop small molecule-based therapeutic?technologies to battle diseases for which current treatment strategies are suboptimal or non-existent. With broad expertise in drug discovery, their efforts are currently centred on the preclinical development of a novel class (DT1) of small molecule inhibitors in cancers of the blood and brain as well as the development of a natural product for topical?treatment of psoriasis and other inflammatory skin disorders.

16-Bit, a start-up founded by two medical doctors from the?University of Toronto’s?Diagnostic Radiology Program, is developing a machine learning algorithm to automate triaging of screening mammograms for breast cancer detection. Their focus is to?utilize modern developments in machine intelligence to improve the accuracy, reliability, and speed of medical image interpretation while decreasing cost and barriers to healthcare.

Diagnostics Development Program at OICR?leader?Dr.?John Bartlett?has developed a diagnostic gene test to predict which breast cancer patients can benefit from anthracycline chemotherapy and which patients can avoid the associated toxicity because the drug may not be effective against their cancer.

The Ottawa Hospital?and the?University of Ottawa?have developed a tumour-destroying virus based on the Vaccinia virus which adds a micro-RNA payload to enhance cell killing against pancreatic cancer. This targeted therapy is expected to be more precise and less toxic than conventional therapies for this difficult-to-treat tumour.

The Prospects Oncology Fund delivers on FACIT and OICR’s shared vision of advancing breakthrough innovations to the benefit of patients and?Ontario’s?knowledge economy. ?Translating early-stage innovations and positioning them to raise additional funding supports?Ontario’s?competitive position as a destination for biotechnology.

Congratulations to all the strong applicants and in particular these outstanding awardees in their quest to make a difference for patients living with cancer.

+++++

Well, that wraps up another episode of Biotechnology Focus radio. I hope you enjoyed it. If you have a story idea or would like to be on the show, please email me at [e-mail]. To see the articles in full check out the website biotechnologyfocus.ca and laboratoryfocus.ca so you don’t miss a beat! Have a momentous week. From my desk to yours – this is Michelle Currie.