Biotechnology Focus Podcast

Q&A with Rory Francis PEI BioAlliance   099| Riding the biotech current to PEI  Welcome to another episode of Biotechnology Focus Radio. I am your host – Michelle Currie. Today, I am joined with a special guest, the executive director of the PEI BioAlliance, Rory Francis, who will be discussing what is happening in the PEI Cluster and with the PEI BioAlliance organization itself.   First, I think it will be important to state what the PEI BioAlliance is and the aim/vision of the organization. Perhaps giving a little bit of the history of the organization as well, then discuss a little bit about what the PEI Cluster is as well.   What is the scale and scope of the PEI Cluster?  Is there a focus of the PEI Cluster? I know that often animal health companies are recruited to the province. Is this something PEI specialises in? What are the incentives that you offer for companies to relocate? What has defined the success of the cluster thus far?  So, coming back to the PEI BioAlliance, what is your operating model? Do you have any strategic priorities? Who is in your company’s portfolio? Who are the major companies and partnerships that should be highlighted? Can you tell me a little bit about your innovation ecosystem? What would you say is the defining success of the organization?     What challenges and opportunities has the organization seen over the years?   What is your strategy for future growth? Does it vary from that of the cluster’s? Incentives?  What are the government’s initiatives? How do they aim to enhance PEI’s assets?   Have I missed anything that you would like to touch on? 

Q&A with CDRD’s President and CEO Gordon McCauley   Taking it up another notch: CDRD discusses the newest addition to their Academy  Welcome to another episode of Biotechnology Focus Radio. I am your host – Michelle Currie. Today, I am joined with a special guest, the president and Chief Executive Officer of the centre for drug research and development, Gordon McCauley, who will be discussing the recent addition of the Executive Institute to CDRD’s Academy.     I will start with asking about the highlights of CDRD – what CDRD does and what they are currently working on now, how they are translating discoveries, etc. (Feel free to elaborate and educate the listeners of Biotechnology Focus Radio of the success and potential of this centre for commercialization.)    I know that you made an announcement earlier this year about adding a new program to the CDRD Academy, but before we delve into that, could you tell me a little bit about the CDRD Academy in general? When and why was it started? What are the benefits of attending the Academy? How many graduates have there been? Is it available to everybody? What are the requirements? What are some of the companies that have arisen in the Canadian life sciences sector from previous graduates?   Now, in the Spring, CDRD unveiled the newest program to the Academy – The Executive Institute – could you tell me more about this latest addition? (What is the duration? How does the collaboration of global training leaders and the not-for-profit Center for Creative Leadership work?)   How is the program funded? (I know Pfizer is, but if you can explain the connection and why they are doing so.) What does Pfizer expect to achieve through this investment?  The members of the first inaugural cohort were released not long ago. I am sure it was a challenging task to narrow down to the 20 executive-level life sciences professionals who were accepted into the program. I am sure there were many great applicants. How did you choose the executives that you did? What was the application criteria and process?   I believe they met for the first time this September 12-13th in Vancouver. How did that first meeting go? Was there a lot of excitement, especially from being chosen in the first cohort? How many times a year will the cohort meet? Will it always be in Vancouver?  What can we expect to see from this executive development program? How will this benefit the life sciences sector and Canada as a whole?   Have I missed anything that you would like to touch on? 

  Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the Canadian biotech rundown from coast to coast. This week there has been some revolutionary research in HIV, and natural killer cells. FACIT – the fight against cancer innovation trust – has invested in three novel cancer therapeutic discoveries, and Oncolytics Biotech enters a clinical collaboration to combat breast cancer. Keep listening to find out more details!  +++++  Researchers at the BC Centre for Excellence in HIV/AIDS (BC-CfE) and Simon Fraser University (SFU), in partnership with University of British Columbia (UBC) and Western University, develop a way of dating “hibernating” HIV strains, in an advancement for HIV cure research in the province.  Published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS), the BC-CfE’s first major scientific contribution to the area of HIV cure research confirms that dormant HIV strains can persist in the body for decades.  Dormant HIV strains, embed their DNA into the body’s cells, tucking themselves away for years – but can reactivate at any time – and are unreachable by antiretroviral treatments and the immune system. This is the reason why HIV treatment needs to be maintained for life.  Dr. Zabrina Brumme, director, Laboratory with BC Centre for Excellence in HIV/AIDS and lead author on the study says that, “If you can’t identify it, you can’t cure it. This research provides further essential clues in the pursuit of an HIV cure—which will ultimately require the complete eradication of dormant or ‘latent’ HIV strains. Scientists have long known that strains of HIV can remain essentially in hibernation in an individual living with HIV, only to reactivate many years later. Our study confirms that the latent HIV reservoir is genetically diverse and can contain viral strains dating back to transmission.”  Dr. Julio Montaner, director of the BC Centre for Excellence in HIV/AIDS  says that, “The BC Centre for Excellence in HIV/AIDS  has consistently been a national and global leader on research on HIV and on the implementation of its pioneering Treatment as Prevention® strategy. The addition of molecular biologist Dr. Zabrina Brumme as director of the innovative BC Centre for Excellence in HIV/AIDS Laboratory ensures the BC Centre for Excellence in HIV/AIDS  will play a significant role in HIV cure research. Curative strategies will need to address this new study’s key findings. I want to acknowledge the study participants and thank them for helping to increase our knowledge on the origins of the latent HIV reservoir.”  Brad Jones, a Ph.D. student with the University of British Columbia (UBC) at BC Centre for Excellence in HIV/AIDS and the first author on the study says that, “By creating family trees of viruses using a technique called molecular phylogenetics, we can reconstruct the evolutionary history of HIV within a person. In essence, we created a highly calibrated ‘time machine’ that gives us a specific time stamp for when each dormant HIV strain originally appeared in a person.”  Through advances in antiretroviral therapy, an individual living with HIV can now live a longer, healthier life on treatment. Treatment works by stopping HIV from infecting new cells. On sustained treatment, individuals can achieve a level of virus that is undetectable by standard blood tests. An undetectable viral load means improved health and that the virus is not transmittable to others—the concept behind Treatment as Prevention®.  Dr. Jeffrey Joy, research scientist at the BC Centre for Excellence in HIV/AIDS and co-author on the study says that “Previous research had already revealed that the HIV reservoir was genetically complex. With our method, we can now understand that complexity with greater granularity, pinpointing exactly when each unique HIV strain originally appeared in a person.”  Dr. Art Poon, assistant professor at Western University’s Schulich School of Medicine & Dentistry, also a co-author on the study, says that, “In order to eradicate HIV from a person’s body, you first need to know the characteristics of HIV in the latent reservoir. We are providing a method for better measuring the timeline of virus latency and evolution within an individual living with HIV.”  “Dating” dormant HIV strains within the viral reservoir involve comparing them to strains that evolved in an HIV-positive person over their entire history of infection.  The BC Centre for Excellence in HIV/AIDS is one of a handful of institutions worldwide capable of such research, thanks to its maintenance of a historical repository of blood specimens from individuals diagnosed with HIV in BC. These specimens date back to 1996 and were originally collected for viral load and drug resistance testing. The BC Centre for Excellence in HIV/AIDS Laboratory has provided HIV drug resistance genotyping for virtually all Canadian provinces and territories since 1998, as well as for many countries worldwide.  This research was funded by the Canadian Institutes of Health Research (CIHR) in partnership with the Canadian Foundation for AIDS Research (CANFAR) and the International AIDS Society (IAS) through its support of the Canadian HIV Cure Enterprise (CanCURE), as well as the US National Institutes of Health (NIH) through its support of the Martin Delaney BELIEVE Collaboratory.  +++++  Immune checkpoint inhibitors are waging a revolutionary war on cancer, but new research challenges the central dogma of how this drug treatment works. This research, published in the prestigious Journal of Clinical Investigation, shows for the first time that often-overlooked immune cells called Natural Killer (NK) cells play a crucial role in responding to checkpoint inhibitors.  co-senior author Dr. Michele Ardolino, a scientist at The Ottawa Hospital and assistant professor at the University of Ottawa  explains that, “Checkpoint inhibitors work by waking up the body’s own immune system and unleashing an immune attack on cancer cells. For many years, everyone assumed that checkpoint inhibitors targeted immune cells called T-cells. But our research shows that they also target Natural Killer cells and these cells play a key role in the how this treatment works.”  Dr. Arolino led the study together with Dr. David Raulet, a professor at the University of California at Berkeley.  Dr. Raulet says that “In the cancer immunotherapy field there has been a singular focus on mobilizing anti-tumor T-cells. We believe that NK cells have an important place at the table. Checkpoint therapy combined with other NK-directed immunotherapies may enable us to target many types of tumours that are currently non-responsive to available therapies.”  T-cells and Natural Killer cells can both recognize and kill cancer cells, but they do so in very different ways. NK cells recognize patterns of changes on cancer cells and are the immune system’s first line of defense. A T-cell, on the other hand, recognizes a single abnormal molecule on a cancer cell and initiates a more focused attack.  In the current study, Drs. Ardolino, Raulet and their colleagues investigated the effect of checkpoint inhibitors in various mouse models of cancer. They found that checkpoint inhibitors could shrink tumours even in mice with no anti-cancer T-cells, meaning that some other kind of cell must be responding to the checkpoint inhibitors. When the mice were depleted of Natural Killer cells, it greatly reduced or eliminated the anti-cancer effect of the checkpoint inhibitors. They also showed that Natural Killer cells produce the same checkpoint receptor molecules that T cells do, inferring they can respond directly to checkpoint inhibitors.  co-lead author Jonathan Hodgins, a PhD student at The Ottawa Hospital and the University of Ottawa says that, “This research helps solve a mystery that’s been seen in the clinic, where certain cancers are very susceptible to checkpoint inhibitors even though their T-cells don’t seem to be activated. If we’re right, Natural Killer cells are probably being activated in these patients.”  Previously, Dr. Ardolino, worked in Dr. Raulet’s lab in California before he was recruited to The Ottawa Hospital and the University of Ottawa in 2016. Together they are now investigating approaches to further enhance the cancer-killing ability of Natural Killer cells.  Dr. Ardolino says that, “My dream is that when people come to the hospital with cancer, we’ll be able to take a biopsy and determine not only the mutations in their cancer, but also profile how their immune system is interacting with their cancer. Then we would give the patient the immunotherapy treatments that is most likely to work for them.”  +++++  As a gateway to the cancer research pipeline in Ontario, and a bridge between public and private sectors with an expanding portfolio of breakthrough innovations, Fight Against Cancer Innovation Trust (FACIT) is committed to supporting Ontario entrepreneurs through the latest round of its Prospects Oncology Fund to continuously identify and advance breakthroughs in science and technology.  FACIT has carefully chosen three novel cancer therapeutic discoveries to receive early-stage capital – biotechnology start-up Talon Pharmaceuticals, the Drug Discovery team at the Ontario Institute for Cancer Research (OICR) and the Centre for Commercialization of Regenerative Medicine (CCRM).  The Prospects Fund provides entrepreneurial scientists with the capital resources necessary to achieve critical proof-of-principle studies for their cutting-edge breakthroughs aiming to benefit future patients.  Talon Pharmaceuticals, through its Multiphore drug design platform, is focused on the discovery, development, and commercialization of medicines designed to save lives and improve patient quality of life. They are developing a novel series of small molecules with an undisclosed mechanism of action applying decades of experience with central nervous system (CNS) drug discovery.  OICR is a collaborative, not-for-profit research institute accelerating the development of new cancer research discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. OICR’s Drug Discovery team and their collaborators at the National Research Council (NRC) will receive funds towards the development of a potentially superior class of antibody-drug conjugates.  CCRM’s mission is to generate sustainable health and economic benefits through global collaboration in cell and gene therapy, and regenerative medicine. CCRM will receive funds towards the development of a universally compatible source for the next generation of CAR-T therapies.  FACIT’s $35-million in investments over multiple years addresses a critical health care seed-stage gap often experienced by Ontario product developers. De-risking innovation sets up successful projects for either company creation or a larger round of financing by FACIT and its investment partners, with over $340-million in follow-on financings to date. FACIT’s maturing portfolio of technology investments anchors companies and jobs in Ontario and reduces the need for entrepreneurs to look south of the border.  David O’Neill, president of FACIT  says that, “Our team is pleased to invest in and work alongside these entrepreneurial scientists, providing capital, industry networks and commercialization expertise, as they advance their therapies closer to clinical development. Capitalizing on the province’s investment in healthcare and scientific collaboration through our strategic partners at OICR is not only good for creating high-skilled jobs but also ensures research undergoes translation to impact the lives of patients with cancer.”  +++++  Oncolytics Biotech Incorporated enters into a clinical collaboration with SOLTI, an academic research group dedicated to clinical and translational research in breast cancer. This clinical collaboration, being sponsored by Oncolytics and facilitated by SOLTI, is a window of opportunity study in the neoadjuvant setting for breast cancer.  Reolysin, (pel-areo-rep), an intravenously delivered immuno-oncolytic virus turning cold tumours hot is under development by Oncolytics Biotech. Patients will receive the appropriate standard of care for their cancer subtype plus pel-areo-rep (or Reolysin with or without the anti-PD-L1 cancer immunotherapy ate-zoli-zu-mab (also known as Tecentriq)). Patients are biopsied on day one, followed immediately by treatment and a final biopsy after three weeks, on the day of their mastectomy. Data generated from this study is intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer sub-type, to support Oncolytics’ phase 3 study in metastatic breast cancer and is expected in mid 2019.  Matt Coffey, president and CEO of Oncolytics Biotech says that they are thrilled to enter into this collaboration with SOLTI and sponsor this window of opportunity study.  They expect that this study will provide additional biomarker and immunological data to support our planned phase three study in metastatic breast cancer. This data should confirm the findings of our phase two study and generate a robust biomarker plan designed to potentially enhance our phase three program. Importantly, it will also generate additional data demonstrating how the promotion of a virally induced inflamed phenotype should synergise with checkpoint inhibitors targeting PD-L1 like ate-zoli-zu-mab.”  The study, facilitated by SOLTI, will be coordinated by Dr. Aleix Prat, head of Medical Oncology at the Hospital Clínic of Barcelona, associate professor of the University of Barcelona and the head of the Translational Genomics and Targeted Therapeutics in Solid Tumors Group at August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and member of Oncolytics’ Scientific Advisory Board. SOLTI has a network of more than 300 professionals, mostly medical oncologists, in over 80 hospitals in Spain, Portugal, France, and Italy. Final study design and other details will be announced upon enrollment of the first patient, expected around the end of 2018 or very early 2019.   Dr. Prat says that, “It has been demonstrated that when reovirus infects a tumor, it promotes the release of immuno-stimulatory signals. This, in turn, results in the upregulation of PD-L1 on tumor cells and the recruitment of inflammatory immune cells like Natural Killer-cells and cytotoxic T-cells to the tumor, which are required prerequisites for checkpoint inhibitors to function effectively.  In short, it turns cold tumours hot. They believe pel-areo-rep can demonstrate the necessary inflamed tumour phenotype to prime tumours for PD-L1 blockade, which could potentially represent a promising form of cancer immunotherapy combination with ate-zoli-zu-mab. Results from this study will seek to establish the virus as an important immuno-oncology agent in breast cancer, which could ultimately support the expansion of pel-areo-rep beyond metastatic breast cancer into first-line therapy.”  +++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for listening! Make sure to check out the articles on the website: biotechnologyfocus.ca. Until the next time, from my desk to yours – this is Michelle Currie.

  Welcome to another episode of Biotechnology focus radio! I am your host – Michelle Currie – here to give you the rundown on what is happening in the life sciences sector from coast to coast. This week brought new collaborations, new cohorts, and new research. Keep listening to find out more!  +++++  As regenerative medicine grows around the world, topping a whopping $36-billion annually and only expected to rise, it comes as no surprise that more and more international collaborations are happening – especially within Canada.  CCRM and the Japanese Society for Regenerative Medicine (JSRM) liaise to advance the field of regenerative medicine (RM) and cell and gene therapies in Canada and Japan, signing a Memorandum of Understanding (MOU) this week at the Annual Meeting of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) in Kyoto, Japan.  Michael May, president and CEO, CCRM says that CCRM’s mission is to generate sustainable health and economic benefits through global collaboration in cell and gene therapy, and regenerative medicine. CCRM is catalyzing a global network of highly integrated commercialization centres working together to enable viable and cost-effective patient access to revolutionary new treatments. The Memorandum of Understanding with Japanese Society for Regenerative Medicine, through its vast research network and industry-enabling activities, is a positive step in that direction.”  The Memorandum of Understanding has been put in place to promote academic and industry partnership in Japan, Canada and internationally to advance the field of regenerative medicine and cell and gene therapies. This will include supporting knowledge translation about technologies, policies (e.g., regulatory and health economics), legal and ethical issues.  Prof. Sawa, president of Japanese Society for Regenerative Medicine.  Says that “There are many obstacles to establish a sustainable business model for regenerative medicine in Japan, as it requires a whole new value chain. Canada’s CCRM has been fostering and promoting a successful commercialization model since its launch. JSRM is proud to announce that we have entered into a partnership with CCRM to develop sound industrialization pathways, learning from CCRM’s excellent model to make regenerative medicine an available treatment worldwide.”  Regenerative medicine – that can be a bit of an umbrella term – includes cell and gene therapy, stem cells, biomaterials, molecules and genetic modification to repair, regenerate or replace diseased cells, tissues and organs. This approach is disrupting the traditional biotechnology and pharmaceutical industries with the promise of revolutionary new cures for devastating and costly conditions such as heart disease, diabetes and cancer.  This sector represents so many potential untapped possibilities. Forecasted to grow to US$49.41-billion by 2021, there were 977 clinical trials in cell, gene and tissue therapy underway worldwide at the close of the second quarter of 2018. The sector achieved the first global approvals and reimbursements for major cellular immunotherapies and gene therapies in 2017, that resulted in record-breaking investment and acquisitions in the sector. This field encapsulates the phrase “the world is truly their oyster”.  +++++  The Centre for Drug Research and Development, Canada’s national life sciences venture, announces the first cohort of the CDRD Academy’s Executive Institute.  Earlier this year, CDRD and Pfizer Canada announced the launch of the Executive Institute under the umbrella of The CDRD Academy. The Institute is a 10-month, focused executive development program open to a limited number of senior-level life sciences professionals annually. It was made possible by a $1M contribution by Pfizer Canada.  After reviewing dozens of applications from across Canada, the Adjudication Committee has selected a cohort of diverse, talented, and forward-thinking individuals that is gender balanced, and represents a variety of personal and professional backgrounds. The following individuals have been accepted into the inaugural 2018-2019 class:  Naveed Aziz, Chief Administrative and Scientific Officer, CGEN – Canada’s Genomic Enterprise, Toronto, ON  Deanna Dryhurst, Chief Scientific Officer, ImmunoPrecise Antibodies Ltd., Victoria, BC  Alexander Graves, Chief Executive Officer, Symvivo Corporation, Vancouver, BC  Allison Gaw, Senior Director, Corporate Development and Intellectual Property, Sierra Oncology, Vancouver, BC  Nataša Jovic, Senior Director, Personal Health, Microbiome Insights, Vancouver, BC  Andrew Knowles, Senior Vice President, Operations, STEMCELL Technologies, Vancouver, BC  Frédéric Leduc, Chief Executive Officer and Co-Founder, Immune Biosolutions, Sherbrooke, QC  Stephanie Michaud, President and Chief Executive Officer, BioCanRx, Ottawa, ON  Carolyn Nalder, Director of Business Operations, Tevosol, Edmonton, AB  Frederic Ors, Chief Executive Officer, IMV, Quebec City, QC  Chris Sinclair, Vice President, Global Commercial Operations, Emergent BioSolutions, Winnipeg, MB  Kimberly Stephens, Chief Financial Officer, Appili Therapeutics Inc., Halifax, NS  Carol Stiff, Senior Director, Sales and Marketing, Santen Canada, Toronto, ON  Jefferson Tea, Vice President, Medical and Scientific Affairs, Takeda Canada Inc., Oakville, ON.  Gordon C. McCauley, president and CEO of CDRD  says that “The core of any business is people and supporting and growing our pool of highly-qualified personnel is critical to drive Canada’s health sciences sector. Through the CDRD Academy’s Post-Graduate and Undergraduate Institutes, we have seen tremendous success over the past 10 years in helping high-potential scientists be more commercially minded. But, with the addition of the Executive Institute to the CDRD Academy, we are now extending our work to also help high-potential business people lead Canada’s science-based businesses of tomorrow; and ensure Canada has the management talent it needs to lead the life sciences world.”  The CDRD Executive Institute program is delivered in collaboration with the not-for-profit Center for Creative Leadership (CCL). The program has been custom-designed and aims to combine researched and proven best practices/principles with targeted industry topics to take participants on a leadership journey. It will blend in-depth assessments, workshops, simulations, challenging assignments and executive coaching.  John Helou, president, Pfizer Canada says that ‘’The CDRD Executive Institute is off to a very strong start. The first cohort of life science executives exemplifies the type of leaders needed for the industry to reach its full potential. We are pleased to help meet the development needs expressed by life sciences industry stakeholders across the country, and to be able to count on the leadership of CDRD to implement concrete measures that will increase the innovative skill level of this vital industry. We are confident that the tailored training and coaching will contribute to the success of many life science organizations in Canada, which is critical for the development of new treatments for unmet medical needs’’.  This course offers a unique opportunity that will further the life sciences community within Canada and potentially bring the sector and consequently, the economy to new heights. The first face-to-face session will happen in Vancouver September 12-13, 2018, with additional workshops to be held in Montreal and Toronto throughout the Winter and Spring 2019.  +++++  Concordia synthetic biology researchers develop a method to fight disease at a genetic level that may revolutionize patient care.  Steve Shih, an assistant professor of electrical and computer engineering in Concordia University’s Faculty of Engineering and Computer Science and with a cross-appointment in biology, is also the founder of the Shih Microfluidics Laboratory.  His team created a system that integrates the automation of complex biology experiments in order to find genes that are related to cancer and kill them before they develop into a potentially fatal disease.  The system is described in a paper published last July by the journal Lab on a Chip.  Shih says that “Finding genes related to cancer is already very difficult. It’s like finding a needle in a haystack, especially with current methods. But hopefully, with this new method, we can expedite the whole process and rapidly find the culprit genes.”  However, finding the genes is one thing. Preventing them from causing cancer is another.  To do that, Shih’s team uses CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) a genetic engineering technique that uses a Cas9 protein (essentially a pair of ‘programmed genetic scissors’) to find a cancer-causing gene and essentially snip it out of the DNA and replace it with a healthier one.  Shih says that “Once both ends of the gene are snipped, it degrades to the point where we won’t have it anymore. Now that gene won’t be able to go through pathways that cause cancer. To be able to do that on a typical platform is very difficult, because we’re dealing with very static, very manual techniques.  “By doing this in an automated way, and by also miniaturizing the scale which we’re working on, we’re able to expedite the whole process. Instead of looking at this process as a matter of weeks, we can look at it in a matter of days.”  The paper’s authors — Hugo Sinha, Angela Quach, Philippe Vo and Shih, all affiliated with Concordia’s Centre for Applied Synthetic Biology — created the first digital microfluidic method that automated arrayed gene editing in mammalian cells.  This involves using tiny amounts of fluid to culture lung cancer cells for up to six days, while at the same time automating gene transfection and knockout procedures.  The whole automation and miniaturization process that they have developed has not only saved them heaps of time, but it has also slightly augmented the efficiency of the knockout procedure itself.  The mission to eradicate cancer has been a personal aspect for Shih, and he believes his work will have direct material benefits for people diagnosed with cancer.  He hopes his project will contribute to the development of personalized platforms for treatment based on their genetic makeup. That platform would be easily transferable and can be set up in any kind of lab or hospital.  In fact, Sinha started a company called DropGenie that will create gene-editing platforms that can bring this idea to realisation.  Despite CRISPR being controversial, Shih believes that only now researchers are reaping its benefits.  He adds that “There still isn’t a killer application for microfluidics, but I think we’ve found it. I think we found that we can use these miniaturized platforms for something that can really save people’s lives down the line. That’s why I say it can be a killer app because hopefully, we’ll be able to eventually kill all cancer cells.”  +++++   Researchers from the Peter Munk Cardiac Centre (PMCC) at UHN suggest that the model used by the Canadian Institute for Health Information (CIHI) significantly underestimates mortality in specialized heart surgery centres. The study’s findings show that CIHI’s model does not encapsulate all the medical problems that patients have when at elevated risk for surgery.  The study, looked at the outcomes of 1,635 cardiac operations performed at the Peter Munk Cardiac Centre between 2013 and 2016. It compared the observed mortality within 30 days of surgery to the predicted mortality rates estimated with either the CIHI administrative data model or the clinical data model used by the Society of Thoracic Surgeons (STS).  Of the 1,635 patients that had heart surgery at the Peter Munk Cardiac Centre, 32 died within 30 days of surgery. These results were in line with the 1.96 per cent mortality predicted by Society of Thoracic Surgeons model – which uses comprehensive data to describe how sick patients are before surgery – for this group of patients. In contrast, the CIHI Cardiac Care Quality Indicator estimated that the mortality rate for these 1,635 patients would be 1.03 per cent.  Peter Munk Cardiac Centre researchers noted that the Society of Thoracic Surgeons model captures seven medical conditions that predict worse outcomes after heart surgery that are not captured in the CIHI model.  These risk factors include whether the patient had heart failure, an abnormal heart rhythm, a recent heart attack, very low blood pressure (shock), needed recent CPR or a mechanical heart pump to live, or had kidney failure. These serious conditions forecast a worse outcome after heart surgery, and are not included in the CIHI database.  Dr. Barry Rubin, medical director of the Peter Munk Cardiac Centre and one of the authors of the study  says that “The predicted mortality of patients undergoing heart surgery based on the Society of Thoracic Surgeons model is similar to what we actually observed,” says. “The failure to include these seven medical conditions causes the CIHI database to underestimate predicted mortality after heart surgery in high risk patients.”  According to Dr. Douglas Lee, senior scientist at the Peter Munk Cardiac Centre and lead author of the study, mortality prediction models – either based on clinical or administrative data – use risk adjustment to account for how sick patients are before surgery at different hospitals. This is necessary as outcomes may vary if leading academic institutions such as the Peter Munk Cardiac Centre operate on sicker patients.  Dr. Lee says that “The CIHI and Society of Thoracic Surgeons models aim to predict outcomes based on the medical complexity and acuity of the patient. In general, academic hospitals take on higher risk cases compared to community hospitals, and good risk adjustment models should factor that in when predicting mortality rates,” explains Dr. Lee.  Incorrect data may lend the impression that there is a higher level of mortality then there should be at the PMCC or other academic centres. This could have the inadvertent effect of causing the highest risk surgery patients to defer potentially-life saving heart surgeries.  CIHI has a legislative mandate to publicly release Cardiac Care Quality Indicator data and has done so since October 2017. Clinicians and researchers have been concerned that the CIHI model may underestimate how sick cardiovascular surgery patients are at Peter Munk Cardiac Centre.  Incorrect data may lend the impression that there is a higher level of mortality then there should be at the Peter Munk Cardiac Centre or other academic centres. This could have the inadvertent effect of causing the highest risk surgery patients to defer potentially-life saving heart surgeries.  The Society of Thoracic Surgeons model considers vital medical conditions to accurately predict how high-risk patients will do after surgery. The CIHI model does not accurately account for complexity of patients, which is recorded in databases specifically designed for the measurement of surgical quality, such as Society of Thoracic Surgeons.  Dr Rubin says that “Clinical data-based models like the Society of Thoracic Surgeons collect much more detailed patient information, but are also more costly to maintain. “Administrative models like CIHI’s continue to play a very important role in assessing quality of care across Canada. We will continue to work in collaboration with CIHI to improve the accuracy of quality report cards that can be used as valid evaluation tools for Canadian hospitals.”  The authors caution that there are limitations to the study, as it was completed in a single centre during a three-year period, observing 1,341 isolated coronary bypass grafts, 143 isolated aortic valve replacements and 151 combined procedures. PMCC researchers declared there were no conflict of interests but would suggest validation of these findings in other academic centres over a longer time interval that would include a larger subset of cardiac operations. This study was supported by the Canadian Institutes of Health Research.  +++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for listening! If you have any questions or comments, please email us at press@promotivemedia.ca . From my desk to yours – this is Michelle Currie.

  Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what is happening in biotech across the country from coast to coast. There have been some interesting developments in the last couple weeks that are changing the scope of the life sciences industry. Some of which I get the pleasure to share with you today. As a first for Canada, Concordia University now houses a facility that will change how synthetic biology research will be conducted; Bioasis Technologies’ promising drug development may have found a way to cross the blood-brain barrier; the Centre for Commercialization of Antibodies and Biologics invests in ImmunoBiochem to advance their therapeutic candidate; and the Canadian government, as well as other investors, allocate $8.8 million to three projects in Ontario.   Keep on listening to find out more details!  +++++  A new facility at Concordia is about to change history. It will house robots that will bring a whole new concept of speed and scale to synthetic biology research.  The Genome Foundry is the first Canadian laboratory of its kind, and amongst only a handful at leading institutions around the world. By automating notoriously labour-intensive lab work, it will eliminate bottlenecks in a rapidly evolving field where the design principles of engineering fuse with the tools of biology to create meaningful synthetic biological systems.  Christophe Guy, vice-president of Research and Graduate Studies at Concordia says that the Genome Foundry solidifies Concordia’s position as the Canadian leader in synthetic biology research and will enable their scientists to work at the cutting-edge while facilitating partnerships with other institutions. Given that Concordia researchers are already engaged internationally in defining the future of this field, they are eager to witness how this new facility will support the transformative work being done at the university.  At the moment, much of the lab work done by synthetic biologists involves moving and combining small amounts of liquids and cells. The Genome Foundry’s robotics will allow for speed and absolute precision, thus greatly increasing the variety and number of experiments that can be completed, and the accuracy with which they can be reproduced.  The Genome Foundry was established with funds from the Canada Foundation for Innovation and the government of Quebec and is part of Concordia’s synthetic biology hub along with the Centre for Applied Synthetic Biology (CASB), the SynBioApps NSERC CREATE program and the soon-to-be-inaugurated District 3 Innovation Centre science hub.  Vincent Martin, co-director of the Centre for Applied Synthetic Biology says that they are thrilled to open the doors of our Genome Foundry. That this is a monumental addition to Canada’s synthetic biology ecosystem. It empowers researchers to navigate uncharted waters alongside international colleagues, and to incubate the future leaders of the field.  The Centre for Applied Synthetic Biology aims to develop high-value applications in human health, agriculture, chemicals and environmental technologies. It also provides a broad range of unique opportunities — such as the recently announced NSERC CREATE SynBioApps program — for training leading experts in the field.  Launching this technology platform also marks Canada’s participation in the next generation of synthetic biology, with Concordia now engaged in directing how this infrastructure will be developed and used on a global scale.  This facility will have real world, potential life-saving capabilities that deliver an innovative scientific approach to create genetic blueprints for individuals, bring more knowledge to researchers on a faster scale, and help physicians diagnose, treat and prevent their patients from contracting future diseases.  +++++  With neurological diseases predicted to rise exponentially across the globe, whether resulting from the extension of life expectancy or aging populations, more novel solutions are necessary so that health care can stay ahead of the game.  Neurological diseases, disorders and injuries – such as Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, brain tumours, and Parkinson’s disease – are some of the leading causes of disability amongst the Canadian population that take a toll not only on the patient and the Canadian health care system, but also have a significant economic impact.  To date, these neurological diseases and disorders have been largely incurable and tend to worsen over time, typically involving invasive procedures by scientists and researchers as they attempt to penetrate the blood-brain barrier. Remarkable as the blood-brain barrier is to neuroscience, it is extremely fickle and highly selective, restricting the paracellular diffusion of water-soluble substances from the blood to the brain. Despite it being nature’s evolutionary way of protecting humans’ greatest asset, it does not come without its faults. Its defensive properties impede the way for medicinal compounds to penetrate the barrier and deliver the potential life-saving properties to their destination point.  Statistics have shown that 1 in 6 will acquire a neurological disease, totalling about 1.25 billion people worldwide. It is for this reason Canadian company Bioasis Technologies Inc. is determined to deliver effective treatments to patients who suffer from one of these diseases.  Vancouver-founded Bioasis has undertaken this challenge by focusing on a single goal: revolutionizing science by transporting therapeutic payloads across the blood-brain barrier and into the brain. They have developed and are in the process of commercializing their proprietary brain delivery technology, the xB3 platform, to make life-saving drugs brain-penetrant and deliver those therapies at a therapeutically relevant dose.  Inception of the company began back in 2007 when researchers discovered an extremely large peptide that was capable of crossing the blood-brain barrier with a substantial amount of cargo. The team did a couple of experiments with Doxorubicin in mice models with cancer that positively showed higher survival rates and became the first proof of concept. The also acquired Trastuzumab data whereby they transferred Herceptin across the blood-brain barrier in sufficient quantities to reduce the number of tumours.  Although researchers have been speculating about less invasive methods that will penetrate the barrier, Mark Day, the president and chief executive officer of Bioasis, comments that the key thing if you have brain cancer is that the only therapeutic benefit will come from a direct infusion into the brain – like drilling a hole in the head – and while some people are trying to inject into the spine and pump it into the central nervous system, none of it has worked. The brain methods do work, so there is at least some data if you inject it that you can get it approved for efficacy for small groups of patients.  Recently, MedImmune, a wholly-owned subsidiary of AstraZeneca, did an independent validation of Bioasis’ xB3 platform technology that transpired incredible results. The study found that the xB3 fusion protein maintained the systemic pharmacokinetics of its payload and had significantly improved and sustained brain exposure of the payload molecule. It provided evidence that Bioasis’ platform technology was recombinant and chemically conjugated drugs across the blood-brain barrier to increase brain exposure.  These data and validation from MedImmune provide promising results that it will work in a phase 1 study. Bioasis figured out that once they attached Trastuzumab to 12 active amino acids (peptide 12aa), 10 times the amount of the drug passed through the blood-brain barrier. Mark Day adds: “What is really important is that once the drug is in the brain it hits the tumour. Looking at these results you can see that there are significant therapeutic doses in the brain and in controlled regions. This shows us that the drug gets into the brain, it gets to the site of action, and binds to those specifically where there are HER2 positive cells.”  Bioasis has four main programs:  xB3-001: Brain Metastases, which is the most common form of brain cancer in adults and is often fatal due to anti-cancer drugs being unable to pass the blood-brain barrier, and is also the program that will progress first to human trials in 2019;  xB3-002: Glioblastoma, one of the most aggressive cancers that originates within the brain, with 80 per cent of diagnosed primary malignant brain tumours as malignant gliomas. It is considered the deadliest form of brain cancer due to its high infiltration of surrounding brain tissue. This program is being done in collaboration with Minerva in Copenhagen;  xB3-007: Neurodegenerative diseases, which entail a progressive loss of function by the neurons in the brain and in being diagnosed at an alarming rate partly due to an aging population; and  xB3-008: Lysosomal storage diseases, which are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies.  If the xB3-001 and xB3-002 programs are successful, it would be the first time in human history that medicine for cancer has been properly received into the brain without having to drill into the patient’s head. This will be a breakthrough in science and open the doors to a floodgate of scientific possibilities.  Bioasis’ technology platform has been so efficacious that there simply have not been any competitors that have been able to keep up. The receptor with which they work with is ubiquitous to the blood-brain barrier walls, providing more possible passageways for medicine to penetrate through. This receptor, even in its natural form, is critical in cleaning out harmful tissues in the brain like Alzheimer’s disease for example and is necessary to maintain brain integrity.   Mark Day adds that the other thing that differentiates them is how they develop drugs. They know that if you engage the target and prove that the target engagement drives biologic effect – to schizophrenia that would be a lowering of dopamine – then you have a good sense of patient population. So, for some of these diseases, there is a very strong genetic basis to them and subsequent diseases that gives them the mechanism to recruit the patient who is most likely to benefit from the medicine in the first tranche.  The proof of principal in the first point, get the proof of concept, on the back of a positive proof of concept then you would go earlier into the diseases. That’s what they can do with our last two neurodegeneration products. Basically, they go into a smaller niche indication, get the proof of concept and then expand it into other disease areas. That’s been the strategy.  With recent editions to their scientific advisory board and looking ahead to put them in the best financial position for Nasdaq, the future looks promising for this biotechnology company. Penetrating the blood-brain barrier has been an arduous task, but if Bioasis is successful, their technology will revolutionize the treatment for neurodegenerative diseases and brain tumours, potentially slowing the progression of disease, and maybe someday offer a cure.  +++++  The Centre for the Commercialization of Antibodies and Biologics (or CCAB) provides a new investment to help advance ImmunoBiochem’s novel breast cancer therapeutic candidate one step closer to the clinic. The agreement marks a first for CCAB as part of its new business strategy, which aims to attract investment to create successful life sciences companies in Canada. CCAB will develop ImmunoBiochem’s lead candidate towards regulatory filings, and merge their business acumen with its research and technical expertise to support the co-development of new biological therapeutics.  CCAB CEO Robert Verhagen says that today’s announcement marks the beginning of a very exciting period of growth. The agreement with ImmunoBiochem is a natural extension of an already fruitful partnership and that they are looking forward to helping the company get to the next crucial stage in the development of this promising anti-cancer therapy. As CCAB continues to expand its mission in this space, they plan on establishing similar partnerships with other emerging companies in the near future.  ImmunoBiochem is developing novel potentiated biologics to treat triple-negative breast cancer (TNBC), an aggressive form of breast cancer for which there are currently no targeted biological treatment options. Earlier this quarter, ImmunoBiochem secured an additional private investment to support its pipeline and entered into a license agreement with the University of Toronto for novel therapeutic antibodies.  ImmunoBiochem’s CEO Dr. Anton Neschadim says that ImmunoBiochem’s highest priority is to make new treatment options available for patients with this difficult-to-treat breast cancer. They have made significant progress and have validated their approach in vivo. CCAB has been tremendously supportive of their work and they are excited that this new agreement will help them advance their lead candidate even further.   Breast cancer is the most common cancer among Canadian women and is the second leading cause of death from cancer. In 2017, 26,300 women were diagnosed with breast cancer and 5,000 women died from the disease. Triple-negative breast cancer accounts for up to 20 per cent of breast cancers and is one of the most heterogeneous diseases, comprising multiple breast cancer sub-types. Consequently, even highly promising treatments that are in late stages of the clinical pipeline are likely to only address the needs of a partial number of triple-negative breast cancer patients. ImmunoBiochem has developed therapeutic candidates that aim to close on this gap by overcoming treatment challenges associated with tumor heterogeneity.  Much of biological therapeutics distinguish cancer cells from normal cells based on proteins differentially expressed on their surface. In solid tumours, most such targets are heterogeneously expressed, impeding complete responses and driving resistance and relapses. ImmunoBiochem is focusing instead on selective targets in the tumour microenvironment that are broadly present and interact with all cells in a tumour, including tumour-supporting stroma. ImmunoBiochem has shown that this approach could be more effective and safer than conventional surface-targeted therapeutics.  This agreement between the two companies has the potential to lead to viable therapeutics that are sorely needed, especially for cancers that have a high rate of morbidity and mortality.  +++++  Genome Canada announces federal funding for seven new projects under the Genome Canada’s Genomic Applications Partnership Program (GAPP), three of which hail from Ontario. This will be driving $2.9 million of federal funding into the province and an additional $5.9 million from investments in the industry, government, and funding partners. For a total of $8.8 million, this could heed rewarding results.  The announcement was made by the Minister of Science and Minister of Sport and Persons with Disabilities. The Honourable Kirsty Duncan, at the Vineland Research and Innovation Centre.  Vineland is partnering with a team of University of Toronto researchers to develop genomics-based technologies that will induce broad-spectrum disease resistance in greenhouse vegetables, allowing new varieties of vegetables to thrive and reducing waste. This will give growers across Ontario and Canada a competitive advantage in a national industry that already generates more than $1 billion annually from retail sales and exports.  In another Genomic Applications Partnership Program project, researchers at McMaster University are partnered with Hamilton-based start-up Adapsyn Bioscience Incorporated to use its proprietary technology platform that combines genomic and metabolomic data with artificial intelligence and machine learning to redefine and accelerate drug discovery for novel treatments of a wide spectrum of diseases. This partnership secured significant foreign and domestic investment and is creating new high-tech jobs in Ontario.  The third Ontario-based Genomic Applications Partnership Program project announced brings together researchers at the Sunnybrook Research Institute and the University of Toronto with Canadian start-up Fusion Genomics to further develop novel infectious disease surveillance tools. Their technology is unique in its ability to detect and genetically characterize infectious viral pathogens through bioaerosols to serve as an early warning for disease outbreaks in both humans and agricultural animals. The development of this pre-emergence environmental detection technology will drive a paradigm shift in public health and animal welfare by offering complete genomic data to anticipate outbreaks, inform disease transmission dynamics and enable vaccine design and production.  Genomic Applications Partnership Program is a program that partners researchers with companies and other end-users who will apply their innovations with the goal of increasing and accelerating the positive social and economic impact of Ontario’s and Canada’s genomics R&D capacity. Since 2013, approximately $86.1 million, including co-funding has been invested in 23 Ontario-based Genomic Applications Partnership Program projects, fuelling innovations, spurring job creation and attracting foreign investment in Ontario’s health, agriculture & agri-food, fisheries, environment and natural resource sectors.  In such an emerging industry, there is nothing better than seeing companies and research succeed. With these recent investments, there is high hope that we will see encouraging results in the future.  +++++  Well that wraps up another episode of Biotechnology Focus radio! Thanks for listening! If you have a story or a story idea, feel free to contact me at press@promotivemedia.ca. Until the next time, from my desk to yours – this is Michelle Currie.

On the line, I have Andrew Casey who is the president and CEO of BIOTECanada. He is responsible for the day-to-day operations of the association and is the primary spokesperson for Canada’s biotech industry communicating on the industry’s behalf of government, regulators, international bodies, media and the Canadian public. He joins us today to share his expertise and what we can expect to see this year during Global Biotech Week.   Show Notes: 1. Canada has always been a powerhouse in biotechnology. The life sciences sector has had such an overwhelming impact on the Canadian economy and shows no sign of slowing down; and with a rapidly growing population and a high demand for resources and better health care, novel ideas are necessary to keep the economy on its feet. Is this something Canada foresaw in 2003 when it created Global Biotech Week? What was the reason Canada created Global Biotech Week initially?  2. Since then it has snowballed to several other countries. Do you expect to see it grow traction in more in the upcoming years? Where has it spread to thus far? Do you find that it brings the global economy together? 3. What can we in the industry expect to come out of this year’s BIOTECanada event? A little birdy told me that BIOTECanada will be announcing the Gold Leaf Awards winners – which are very prestigious – that represent the companies and individuals who have made significant contributions to Canada’s biotech ecosystem. Any chance you could give us a sneak peak at some of the nominees?  4. Gauging by how Canada has done so well in the past, but now has more extensive global competition, how can Canada prove that we are at the forefront of this monumental shift to feed, fuel and heal the world? And how do you think the world can conjoin together to face and find cures for some of the world’s most devastating and debilitating diseases? 5. When Budget 2018 was released, Bill Morneau, the Canadian minister of finance, stated that that was the largest investment in fundamental and discovery research in Canadian history. What have you seen come from that so far? What do you think we can expect to see? How does this position Canada as a world leader in biotechnology? What do you predict to see happening in the future? 6. Is there anything else I have missed that you would like to touch on? Well that concludes another episode of Biotechnology Focus radio. I would like to thank our guest again, Andrew Casey for being with us today and thank our listeners for their continued enthusiasm of the life sciences sector in Canada. I hope you all have a wonderful week. From my desk to yours – this is Michelle Currie.

  This week brings around new research from an international study that claims an average sodium intake does not harm your health; NSERC grants 1.65 million for a new biomedical technology program; Prometic Life Sciences elucidates the mechanism of action of their proprietary drug; and Milestone Pharmaceuticals randomises their first patient in their phase 3 clinical trial.   Keep on listening to hear all the juicy details!   +++++  No need to fret when you ask someone to pass you the salt at the dinner table anymore. New research by scientists of the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences as well as researchers from 21 countries suggests sodium intake does not increase health risks except for those who eat more than five grams a day – an equivalent of 2.5 teaspoons.  This large-scale international study expresses for most individuals that this is good news. Any health risk of sodium consumption is virtually eliminated if people improve their diet quality by adding fruits, vegetables, dairy foods, potatoes, and other potassium rich foods.  The study followed 94,000 people, aged 35 to 70, for an average of eight years in communities from 18 countries around the world and found there an associated risk of cardiovascular disease and strokes only where the average intake is greater than five grams of sodium a day.  China is the only country in their study where 80 per cent of communities have a sodium intake of more than five grams a day. In the other countries, most communities had an average sodium consumption of 3 to 5 grams a day.  The World Health Organization recommends consumption of less than two grams of sodium — that’s one teaspoon of salt — a day as a preventative measure against cardiovascular disease, but there is little evidence in terms of improved health outcomes that individuals ever achieve at such a low level.  The American Heart Association recommends even less — 1.5 grams of sodium a day for individuals at risk of heart disease.  Andrew Mente, first author of the study and a PHRI researcher says, “Only in the communities with the most sodium intake — those over five grams a day of sodium – which is mainly in China, did we find a direct link between sodium intake and major cardiovascular events like heart attack and stroke. In communities that consumed less than five grams of sodium a day, the opposite was the case. Sodium consumption was inversely associated with myocardial infarction or heart attacks and total mortality, and no increase in stroke.”  Researchers found that all major cardiovascular problems – including death – decreased in communities and countries where there is an increased consumption of potassium which is found in foods such as fruits, vegetables, dairy foods, potatoes and nuts, and beans.  Martin O’Donnell, co-author of the report, an associate clinical professor of medicine at McMaster says that most previous studies relating sodium intake to heart disease and stroke were based on individual-level information, and that public health strategies should be based on best evidence.   Their findings demonstrate that community-level interventions to reduce sodium intake should target communities with high sodium consumption and should be embedded within approaches to improve overall dietary quality. There is no convincing evidence that people with moderate or average sodium intake need to reduce their sodium intake for prevention of heart disease and stroke.  This study lends a hand to simmer down those creeping thoughts of sodium consumption and health issues. Of course, it is still best to use in moderation; but next time someone asks you to pass the salt, you can now more comfortably allow your worry to subside.  +++++  Medical innovations improve and save lives. It for this reason that Canada invests so heavily into the health and life sciences. But when it comes to health technology, innovative designs like prosthetic limbs or pacemakers must be designed by a special type of engineer – one who solve engineering problems and can identify medical technology needs.    Catherine Burns, professor of systems design engineering and executive director of the Centre for Bioengineering and Biotechnology, has been awarded a Collaborative Research and Training Experience Program (CREATE) grant to establish a biomedical engineering graduate program that will help produce this type of engineer. The $1.65 million grant awarded by the Natural Sciences and Engineering Research Council of Canada (NSERC) will help fund a new program in global biomedical technology research and innovation at Waterloo starting in the fall of 2018, the only one of its kind in Canada.  Burns says that most students come out of biomedical engineering graduate programs as great researchers, but not necessarily with a good understanding of how the industry works. That this program will produce students who know both the research side and the business side of the industry.  To understand the needs of medical technology users, students will get out into the field to work alongside clinicians and patients to better understand real-life scenarios before developing solutions.  Grand River Hospital is one of the partners to the program, as well as Starfish Medical and Synaptive Medical – both of which are very successful Canadian medical device companies.  The curriculum at Waterloo will include clinic and industry internships, commercialization courses, international exchanges, and professional skills workshops. Students will graduate knowing how to work with patients and clinicians with understanding of medical device regulation. They will also have the skills and industry contacts in place to help secure jobs in the biomedical industry or commercialize their own inventions.  Charmaine Dean, the vice president of university research  says that the technical expertise, professional skills, and interdisciplinary experience students gain in this program will produce biomedical engineers capable of transforming the Canadian health technology landscape and is another step in growing Waterloo’s role in the biotechnology and research ecosystem.  There is a proposed initiative for the program at Toronto Western Hospital, where a Critical Care physician manages a large amount of data on brain injuries. The goal would be to integrate the data with data from laboratory and patient records, which will provide new insights into the complex physiological relationships in brain injury patients. Students in the program will work with the physician to acquire an understanding of brain injuries, and then develop a data integration solution.  Each student will be part of a team that includes a research supervisor, a clinician, and the manager of a biomedical engineering company. Before commencing their research, students will need to prove that they’ve spent time with clinicians and patients in settings relevant to their area of research. This will help ensure that the solutions they develop are viable and easier to commercialise.  Overall, this one-of-a-kind program will continue to make Canada an economic powerhouse and punch above its weight in health and life sciences.  +++++  Prometic Life Sciences Inc. announces the publication of a paper that further elucidates the mechanism of action of its lead drug candidate, PBI-4050, on liver fibrosis in the Journal of Pharmacology and Experimental Therapeutics.   The drug’s clinical activity has already been shown to significantly reduce liver and cardiac fibrosis in patients in the ongoing Phase 2 clinical trial in patients with Alström syndrome.  Dr. Lyne Gagnon, senior author of the paper and Prometic’s vice president of R&D says that studying the mechanism of action of PBI-4050 in liver diseases, including non-alcoholic steatohepatitis (NASH), has clearly demonstrated that PBI-4050 acts through a major signaling AMPK pathway, thus linking metabolism to fibrosis. The data shows the potential therapeutic effects of PBI-4050 in liver fibrosis and non-alcoholic steatohepatitis.  There are several stages of liver fibrosis, and if left untreated or without changing significant lifestyle choices, may lead to liver cirrhosis.  Pierre Laurin, chief executive officer of Prometic adds that they have seen the benefits of PBI-4050 in reducing liver fibrosis in Alström syndrome patients. With this further validation that the signaling pathway targeted by PBI-4050 is indeed at the core of the genesis of fibrosis in the liver, they are very confident about its potential to address fibrosis-related conditions such as Alström syndrome, and non-alcoholic steatohepatitis. We look forward to initiating our Phase 3 pivotal clinical trial for PBI-4050 in IPF and expanding the program in Alström syndrome.”  +++++  Milestone Pharmaceuticals, a clinical-stage cardiovascular company, randomises their first patient in its Phase 3 clinical study of etripamil. Etripamil is a new investigational, rapid-onset, short-acting calcium channel blocker administered intranasally by the patient designed to terminate paroxysmal supraventricular tachycardia (PSVT) episodes wherever they occur.  paroxysmal supraventricular tachycardia is a recurring and sporadic heart arrhythmia caused by abnormalities in the cardiac conduction system. The current standard of care to terminate these episodes is intravenous medication delivered in the emergency department.  The Phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven study is planned to be conducted in more than 50 cardiology centers in the United States and Canada and will enroll up to 500 patients. Following an in-office test dose of etripamil, patients will take home either 70 mg of etripamil or placebo for when a paroxysmal supraventricular tachycardia episode occurs. Upon onset of an episode, patients will apply a wireless cardiac monitor to their chest to record their heart rhythm, perform a vagal maneuver, and if symptoms persist, administer study drug.  Bruce Stambler, MD, FHRS, Piedmont Heart Institute says that the design of the NODE-301 study of etripamil will allow them to obtain more clinical evidence of the benefits of this potential treatment for paroxysmal supraventricular tachycardia in an outpatient, real-world setting. paroxysmal supraventricular tachycardia is an unpredictable disorder and the potential for a fast-acting therapy to resolve the symptoms of paroxysmal supraventricular tachycardia wherever the episodes occur could significantly reduce the burden this condition puts on patients and the health care system.  The primary endpoint of the study is time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm after the administration of study drug as confirmed by a central independent adjudication committee. Secondary study endpoints include relief of symptoms commonly associated with an episode of paroxysmal supraventricular tachycardia such as heart palpitations, chest pain, anxiety, shortness of breath, dizziness, and fainting.  Francis Plat, MD, Milestone’s Chief Medical Officer  says that the initiation of the NODE-301 study is an example of our ongoing commitment to improve the lives of patients with paroxysmal supraventricular tachycardia. Etripamil, if approved by regulatory authorities, could empower patients to take control of this anxiety-producing arrhythmia without being reliant on chronic medications or trips to an acute-care facility for treatment.  The study will enroll patients at least 18 years of age with a documented history of paroxysmal supraventricular tachycardia. Patients receiving study treatment in NODE-301 will be eligible to participate in an open-label extension study (NODE-302) where etripamil will be provided for subsequent paroxysmal supraventricular tachycardia episodes.  There are well over a million people in the US living with paroxysmal supraventricular tachycardia, resulting in hundreds of thousands of emergency department and doctor’s office visits each year. There are countless other patients who exist and don’t seek care, suffering through their episodes in silence as the current approved treatment options are unpleasant, inconvenient, and/or costly.  Providing a way to self-manage paroxysmal supraventricular tachycardia episodes could offer immediate relief for those living with this arrhythmia.  +++++  Well that’s it for this week! If you have a story idea, please feel free to reach out to me at press@promotivemedia.ca and be sure to check out the stories in full at our website biotechnologyfocus.ca. Until next time, from my desk to yours – this is Michelle Currie.

  Even though we have been having a terrific summer, innovation doesn’t just stop when the sun is beckoning, and the cottage is calling our name. It persists through rain and shine, and never has that been truer. Keep listening to find out what’s new this week!  +++++  Vasomune Therapeutics, a Toronto-based spin-out from Sunnybrook Research Institute and MaRS Innovation, and AnGes, Inc., a Japan-based biotechnology company focused on developing biotherapeutics, sign an innovative multi-million-dollar global Co-Development Agreement for the development and commercialization of therapeutics treating diseases associated with blood vessel dysfunction and destabilization.  The collaboration will advance Vasomune’s peptide-based Tie2 receptor agonist program, initially for the treatment of critical care indications, including Acute Respiratory Distress Syndrome (ARDS), into clinical development with the expectation of initiating clinical trials in 2020. Acute Respiratory Distress Syndrome is a critical care indication with a significant unmet medical need as there are currently no approved therapeutics.   With such a foundational mechanism involved in multiple disease states, the parties have the option to co-develop the compounds for additional indications associated with vascular dysfunction and leakage. These indications include asthma, atopic dermatitis, glaucoma and vascular complications of diabetes.  Parimal Nathwani, president and CEO of Vasomune Therapeutics says, “Vasomune is enthusiastic to combine our technology, scientific and preclinical expertise with the significant development capabilities and track record of our colleagues at AnGes through this unique partnership structure to maximize the opportunity for a Tie2 receptor agonist to benefit patients. AnGes’ commitment to developing truly novel biotherapeutic medicines directly aligns with Vasomune’s objectives.”  Under the terms of the agreement, AnGes will provide Vasomune with multi-million-dollar co-development contributions including upfront and clinical milestone fees. The initial objective of the partnership is to achieve human proof of concept in Acute Respiratory Distress Syndrome, which alone is could potentially be a US$2.5 billion market opportunity worldwide.  Ei Yamada, president and CEO, AnGes, states, “We are truly impressed by the quality of the research derived from Sunnybrook Research Institute and the unique partnership with MaRS Innovation that has created and advanced Vasomune Therapeutics. This program represents a significant commitment by AnGes to advance and develop truly innovative biotherapeutics towards commercialization for the benefit of patients.”  The partnership provides the option for continued co-development through to commercialization and expansion to other indications. The parties will share equally in all expenses and all proceeds including milestone and royalty payments from any third-party licensing transaction. Development and commercialization of the program will be managed through joint committees organized by the two companies.  Rafi Hofstein, president and CEO of MaRS Innovation  says, “We are honoured to have AnGes validate the strength and translatability of Vasomune’s science led by Dr. Paul Van Slyke, chief scientific officer and co-inventor. This unique partnership has attracted foreign capital and expertise to allow Vasomune, a Canadian born company to grow and scale in Canada and maintain the legacy of the late Dr. Daniel Dumont.”  +++++  Even as brief as two weeks of inactivity as an aging adult might put you at risk of developing type 2 diabetes according to a study conducted at McMaster University.  Not only did an abrupt, brief period of inactivity hasten the onset of the disease and elevate blood sugar levels among pre-diabetic patients, but researchers reported that some study participants did not fully recover when they returned to normal activity for two weeks.  The findings are published online in The Journals of Gerontology.  Lead author of the study, Chris McGlory, a diabetes Canada research fellow in the Department of Kinesiology at McMaster University says, “We expected to find that the study participants would become diabetic, but we were surprised to see that they didn’t revert back to their healthier state when they returned to normal activity.”  Participants were asked to reduce their daily steps to no more than 1000 steps per day, the equivalent of being housebound due to factors such as illness. Their steps and activity were measured using pedometers and specialized activity monitors, while researchers tested their blood sugar levels and took blood samples during the two-week period.  The results imply that seniors who experience periods of physical inactivity from illness, hospitalization and bed rest are more likely to suffer detrimental consequences to their overall health.  Stuart Phillips, the professor in the Department of Kinesiology at McMaster who oversaw the research explains, “Treatment of type 2 diabetes is expensive and often complicated. If people are going to be off their feet for an extended period they need to work actively to recover their ability to handle blood sugar.”  According to the most recent statistics from the Centres for Disease Control and Prevention, more than 30 million Americans have diabetes and more than 84 million are prediabetic.  In Canada, Type 2 diabetes is one of the fastest growing diseases, with nearly 60,000 new cases reported each year, according to the Public Health Agency of Canada.  It is the sixth leading cause of death and the leading cause of adult blindness and adult amputation.  In order for pre-diabetic older adults to recover metabolic health and prevent further declines from periods of inactivity, strategies such as active rehabilitation, dietary changes and perhaps medication might be useful.  This research has shown that within days of the onset of inactivity, there are substantial reductions in skeletal muscle mass, strength and a rapid onset of insulin resistance, which is a common feature of type 2 diabetes.  +++++  The Canadian Institutes for Health Research awards the University of Saskatchewan over $2.4 million for indigenous health care, stroke recovery, and cancer research.  Karen Chad, the vice-president of research says, “This major health funding will accelerate research into cancer, stroke, and infectious diseases such as HIV, improving the lives of patients and their families. This funding success also underscores our commitment to community-based research and to incorporating Indigenous ways of knowing.”  Dr. Alexandra King, Cameco chair in Indigenous health, is leading the two projects with an Indigenous focus: studying the potential benefits of peer support for Indigenous women who have HIV or hepatitis C and examining how to improve health and wellness in older Indigenous women living with HIV.  Saskatchewan has the highest rate of HIV in Canada––2.3 times higher than the national diagnosis rate, according to the provincial government. HIV and hepatitis disproportionately affect Indigenous peoples and particularly, Indigenous women.  King will observe the role of a “peer navigator” to determine if the support they extend to indigenous women living with HIV and hepatitis helps them better connect and receive backing from the health care system. Peer navigators are individuals who have gained the wisdom of specific conditions through lived experience, and who receive further training and education on health and related issues.  King says, “Within most Indigenous communities, we put great value on wisdom gained through lived experience. Peer navigators relate to patients in ways that physicians and nurses or other health professionals can not. It just makes sense to have peers involved in health care.”  King’s other study will involve engaging older Indigenous women who are living with HIV to collaboratively create and implement a wellness pilot project based on their self-defined programming needs in five communities in Saskatchewan and British Columbia.  King goes on to say that “Indigenous health research long ago embraced many of the same principles that patient-oriented research now does, in that people with lived experience of a health condition are involved throughout. We’re incorporating culture and ceremony as part of the research process, so the research itself is healing for participants and for the researchers.”  Microbiology and immunology researcher Linda Chelico will lead an $822,000 project to examine the activity of a specific family of enzymes that protect the body against viruses. But if there are too many enzymes, it could lead to a mutation in healthy DNA cells potentially leading to cancer.  Chelico will determine in breast cancer cells whether the enzymes can be used to predict cancer outcomes, be targeted to block cancer starting or progressing, or be used to suppress cancer evolving.  Pharmacy and nutrition researcher Phyllis Paterson is using a rat model to examine how better, more protein-rich nutrition after a stroke can bolster recovery of the brain and leg muscles, in part of a combination of therapies.  Protein-deficient nutrition affects 20 to 35 per cent of patients one-week post-stroke, and up to half of all patients during rehabilitation are protein-deficient due to challenges such as physical and mental disability, and difficulty swallowing.  Overall, the CIHR grants will pay for 14 staff positions and funding of six graduate students and one post-doctoral fellow.  +++++  Antibe Therapeutics Incorporated., a company developing safer therapeutics for pain and inflammation, updates its clinical development activities for its lead drug, ATB-346.  ATB-346 is a hydrogen sulfide-releasing derivative of naproxen. Nonsteroidal Anti-inflammatory Drugs are the most commonly used therapy for osteoarthritis, rheumatoid arthritis, gout, and general pain reduction, but their use is associated with a high rate of gastrointestinal ulceration and bleeding. Patients with these conditions would benefit greatly from an effective, non-addictive, Gastrointestinal-sparing anti-inflammatory/analgesic agent such as ATB-346.  The Phase 2 dose-ranging, efficacy study remains on track to commence this quarter. Furthermore, Antibe has been pursuing additional development activities that are required for regulatory approval and of strategic value to future partners. The company recently completed a series of animal metabolism studies that have provided key insights on the pharmacokinetic profile of ATB-346. These insights can now be leveraged to better determine the doses and dosing regimens to be used in the upcoming Phase 2 study.  Dan Legault, Antibe’s CEO, says, “Based on the recently reported COX inhibition data and metabolism insights, we have augmented our Phase 2 dose-ranging, efficacy study for ATB-346 to include two protocols. The first protocol will expand upon the metabolism findings which should enable us to better select the optimal doses for the subsequent protocol. Although this modestly extends the timelines of the overall study, it provides a faster path to obtaining the comprehensive package of efficacy and metabolism data that is required for regulatory bodies such as the FDA and valued by global partners.”  The upcoming Phase 2 study will now include a metabolism protocol that will directly inform the dosing cohorts to be used in the subsequent dose-ranging, efficacy protocol. Therefore, the updated development plan will include two parts:  Part 1: Characterization of Metabolites. The primary objective of the metabolism study is to determine the principle metabolites of ATB-346 in humans and characterize their activity and pharmacokinetic profile. The study will be conducted in approximately 25 healthy volunteers and is anticipated to commence this quarter and should take 8-10 weeks to complete.  Part 2: Validation of Effectiveness. The dose-ranging, efficacy study will be conducted in approximately 200 osteoarthritis patients. The primary objective of the study is to evaluate the efficacy of ATB-346 in reducing pain at three doses (versus control) and establish the lowest effective dose. The profile of each ATB-346 dosing cohort will be finalized based on the findings of the above-mentioned metabolism protocol. A top-line data read-out from this study is anticipated in second quarter of 2019.  Antibe expects that the full Phase 2 study with the metabolism protocol will cost roughly $3 million and will be funded with cash-on-hand. Clinical studies have indicated that ATB-346 is much more potent than naproxen and proposes that that one or more active metabolites contribute to the mechanism of action.  +++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for listening! Hope you all had a chance to get outside this past long weekend and take advantage of what’s left of summer. Maybe innovation will strike, and it will be your story I’m reading next! For the stories in full, check them out at biotechnologyfocus.ca. Until next time, from my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio. I am your host – Michelle Currie – here to give you the lowdown on the Canadian biotech scene. This episode I will be discussing how new biomarkers found in maternal blood could prevent stillbirth, a new therapy for patients with partial spinal cord injuries, an investment from the Government of Canada, and Inversago closes their first series A financing round.   +++++  Researchers from the University of Alberta suggests new biomarkers found in maternal blood may help prevent stillbirth.  David Wishart, lead author and professor in the Department of Biological Sciences says, “When we started analyzing the blood of women who experienced stillbirth and compared them to healthy women, we noticed there’s a chemical difference. This suggested that we could predict and potentially prevent stillbirths.”  Using a mass spectrometer, Wishart and his colleagues identified four chemicals that showed up repetitively in mothers who experienced stillbirth. Combining this with demographic information about the mothers, the researchers discovered biomarkers for predicting signs of first-trimester stillbirth, including a fifth, previously unknown blood chemical called verruculotoxin.  Wishart explains that “Verruculotoxin is likely produced by microbes and fungi. This is intriguing because there’s anecdotal information about people living in certain areas, where there’s high mold, having a high incidence of stillbirth.”  Using this approach, scientists could develop tools and technology to screen for preventable illnesses that affect both women and children, explained Wishart.  Wishart says, “This research is the tip of a bigger iceberg. By looking at the chemicals in the mother’s blood, we can actually identify the risk for not just stillbirth, but a whole range of other conditions both for the mother and the fetus.”  Due to verruculotoxin being a newly discovered substance, further investigation and testing is required before a definite relation to stillbirth can be confirmed.  Previous research into predicting stillbirth has focused on genetics. Focusing on chemicals within the body gives scientists a clearer view of the potential causes and reasons. The technique also opens doors to other risk-related conditions that can happen during pregnancy.  Stillbirth is typically defined as fetal death at or after 20 to 28 weeks of pregnancy. It results in a baby born without signs of life. The term is in contrast to miscarriage which is an early pregnancy loss, and live birth where the baby is born alive, even if it dies shortly after.  +++++  New research from the University of Saskatchewan has scientists excited about the potential of a new therapy called acute intermittent hypoxia (AIH) for patients with partial spinal cord injuries.  AIH therapy involves repeated exposure to low oxygen (hypoxic) levels for brief periods. This action triggers a chain of events in the nerve cells or neurons as they react to the mild stress.  Valerie Verge, a professor of anatomy and cell biology in the College of Medicine says, “The acute intermittent hypoxia  AIH alerts the cells that they’re under stress. The cell adapts by turning on specific genes and creating specific proteins that help the cell to survive the stress. They induce a strengthening of the existing neuronal connections which is referred to as plasticity.”  As director of the Cameco MS Neuroscience Research Center, Verge has a keen interest in neurological research. She shares this passion with Dr. Gillian Muir, a professor at the Western College of Veterinary Medicine (WCVM) and the co-principal investigator in a recent study published in PLOS ONE.  While Verge’s focus is on the cellular level, Muir is an expert in behavioural recovery after injury. She has collaborated on studies with professor Gordon Mitchell, a noted neuroscientist at the University of Florida, and she has been involved in multiple studies monitoring the functional recovery that occurs when AIH acute intermittent hypoxia  therapy is combined with rehabilitative training in patients with spinal cord injuries.  Muir says, “The focus of this recent study was to look at what was changing in the cells of these animals in response to both the hypoxia exposure and the rehabilitative training. We looked for hypoxia-associated proteins, evidence that the cells were responding to the low oxygen, and we also looked for proteins associated with the plasticity—the proteins involved in strengthening connections between neurons.”  The study used two groups of rat models with partial spinal cord injuries that received seven days of rehabilitative motor therapy, with only one group reviving the AIH acute intermittent hypoxia  therapy along with the daily regime.  Each AIH treatment consisted of 10 five-minute cycles where the animals breathed hypoxic air (11 per cent oxygen) alternating with normal air (21 per cent oxygen). The research team compared the abilities of both groups each week as they performed specific motor tasks that had been mastered before the injury, and then they compared the cells in the spinal cords of both groups of animals. Results confirmed that AIH leads to increases in the amount of specific proteins within cells linked to hypoxia and plasticity. They also observed notable improvement in the functional abilities of the group that received both AIH and rehabilitative therapy.  Muir says, “We think that this combination of treatment is important because the AIH makes the cells more accessible to plasticity—that is, more amenable to making stronger connections with other neurons. The rehabilitation training activates the correct neural pathways and ensures that the appropriate neural circuitry becomes stronger.”  There have already been clinical and preclinical trials done in the States demonstrating that patients with spinal cord injuries who received AIH therapy could walk farther for longer and with improved ability.  A noteworthy finding of the current study was evidence that the proteins connected with plasticity were increased in areas of the spinal cord other than just the injury site—an indication that hypoxia triggers a reaction from neurons in other parts of the body, including the brain. Since AIH treatments expose the whole body to hypoxia, it’s possible that the nerve cells of the peripheral nervous system and the brain are also reacting to the low-level stress by creating the proteins associated with plasticity.  Verge and Muir are optimistic that AIH therapy will have a positive impact on a large spectrum of injuries and conditions that affect the nervous system; and although it is still too early to say, this study prompts further questions to the possibilities of AIH therapies and whether it can enhance the nervous system or even repair damaged cells.  +++++  There is a wide spectrum of health conditions from diabetes, mental health, and cancer that affect the Canadian population. These diseases pose a serious health risk to patients and the Canadian health system, and novel solutions are sorely needed. Promising advances may soon be close at hand thanks to an investment from the Government of Canada and several provincial and international partners and research institutions that will allow scientists to test-drive new ways to treat disease and improve patient care to see if they work in the real world.  Sonia Sidhu, Member of Parliament for Brampton South, on behalf of the Honourable Ginette Petitpas Taylor, Minister of Health, announced an investment from the Government of Canada, through the Canadian Institutes of Health Research, of $9.3 million while visiting St. Michael’s Hospital, where three of the research projects will be based.  The program, known as the Innovative Clinical Trials Initiative, will include additional funding of $13.3 million from partners, for a total investment of $22.6 million.  The investment will provide support over the next four years to seven research projects tackling a range of health issues that matter to Canadians:  -Reducing the incidence of diabetic foot ulcers – one of the most common and feared side-effects of diabetes, which, if left untreated, can lead to amputations;  -Reducing the number of unnecessary x-rays and pre-operative tests administered to patients;  -Supporting doctors to improve opioid- and antibiotic-prescribing practices;  -Reducing childhood obesity by re-examining the consumption of low-fat versus whole milk;  -Improving care and outcomes for patients admitted to intensive care units;  -Helping patients with multiple complex conditions navigate the health care system; and  -Improving care and recovery for young adults experiencing their first episodes of psychosis, such as schizophrenia.  The Honourable Ginette Petitpas Taylor, Minister of Health says, “Our Government proudly supports science because it has the power to change lives. The projects we are investing in today bring the promise of new treatments and improved quality of life for people with diabetes and mental illness, new insights into tackling childhood obesity, and new tools for health professionals to make the health care system more sustainable and work better for patients.”  Life sciences is an industry that is filled with innovation and offers much economic promise for governments who desire to grow a knowledge-based economy.  +++++  Inversago Pharma recently closed their first Series A financing round at $7 million. They join Accel-RX’s growing portfolio of promising next-gen Canadian start-ups, as well as co-investors Genesys Capital, AmorChem, Juvenile Diabetes Research Foundation T1D Fund, Anges Québec Capital as well as several angel investors.  Inversago is developing new generations of CB1 receptor inverse agonists. First generation CB1 blockers were previously in development for a range of metabolic conditions but were permeable to the blood-brain barrier and targeted brain CB1 receptors. This brain occupancy led to psychiatric adverse events which caused the termination of all CB1 inverse agonist programs.  The company’s technology, based on the work by CB1 world expert, George Kunos at the National Institutes of Health, has demonstrated that peripherally restricted CB1 blockade in preclinical models provides an equivalent therapeutic potential to treat conditions such as Obesity, NASH, type-1 and 2 Diabetes, Liver & Lung Fibrosis, without causing the CNS or behavioural effects associated with the earlier generations of CB1 blockers. The proceeds from this first round of financing will allow Inversago to focus on its first target indication, Prader-Willi Syndrome, an orphan disease that often leads to obesity and type-2 diabetes, as well as explore potential in type-1 diabetes.  Accel-Rx president and CEO, Natalie Dakers says, “Inversago’s technology could provide game-changing treatments for a number of metabolic diseases with few treatment options. Their novel approach to resolving prohibitive concerns involving the brain associated with this class of drug meshes with our investment philosophy of backing companies whose solutions are both innovative and designed for broad impact.”  This is Accel-Rx’s tenth investment in a portfolio that includes disruptive treatments and technologies to innovative approaches to neurodegenerative diseases, including Alzheimer’s and Lou Gehrig’s Disease.  Inversago founder and CEO, François Ravenelle says, “We are pleased to join the Accel-Rx portfolio of innovative companies and are grateful for their help in securing the two lead investors and spearheading the diligence efforts. Their involvement was instrumental in the success of this round and will enable the company to advance its program into clinical trials.”  Since 2014, Accel-Rx has screened over 200 early-stage companies from across Canada, selecting ten for investment and attracting an additional $44.6 million in co-investment thereby leveraging their initial capital outlay by more than 9X.  +++++   Well that wraps up another episode of Biotechnology Focus radio. Make sure to tune in next week to hear what is going in the life sciences sector from coast to coast. From my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio. I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene! Coming up we have some inspiring research from the University of Alberta regarding viral pathogen treatment; McMaster researchers have a new hypothesis on Huntington’s Disease; RepliCel solidifies co-development deal in Greater China; scientists discover a way to genetically screen for acute myeloid leukemia; and putting Canada in the limelight when it comes down to artificial intelligence and deep learning.   Keep on listening to find out more of the details!  +++++  The University of Alberta appears to have hit the nail on the head yet again. With so much inspiring research coming out of this campus, it should come as no surprise that they have made a significant discovery that has the potential to treat viral pathogens such as the Zika virus and respiratory syncytial virus (RSV).  Scientists from UofA discovered a new and promising class of chemical compounds that is comparable to the naturally occurring isatisine A, an antiviral originally found in traditional Chinese herbal medicine.  Fred West, a professor in the Department of Chemistry, who led the discovery along with RSV researcher David Marchant, a professor in the Department of Medical Microbiology and Immunology, says, “This is both a remarkable scientific discovery and also something that has the potential to positively affect not only global health but also the economy of Canada.”   West and Marchant worked in conjunction with Zika expert and cell biologist Tob Hobman, who is also a professor in the Faculty of Medicine & Dentistry at the University of Alberta. They tested the compound against potent viruses, such as Zika and respiratory syncytial virus , that yielded remarkable results. The compound was active and effective against both viral infections.  The Zika virus, which is a mosquito-borne pathogen, began wreaking havoc in May of 2015 after it had been identified as the culprit behind an outbreak of prenatal defects across South America. It coincided with a 2,700 per cent increase in Brazil from reported cases of microcephaly, an often fatal congenital condition associated with incomplete brain development in newborns.  Whereas, relatively unheard of respiratory syncytial virus poses a greater threat to infants, the elderly and those with compromised immune systems. This virus is responsible for up to 30 per cent of hospitalized respiratory cases in any given year.   West adds, “What we aim to do is further refine this compound to keep the elements that make it medically active and build in the structural components that make it possible for patients to consume in drug form. We are approaching that point.”  The next stage of drug development is already underway, and with Marchant’s new company Antibiddes Technologies Inc. ready to license the intellectual property and begin commercialisation, this is a promising development that could change the face of viral pathogen treatment.  ++++++  McMaster researchers develop a new theory regarding Huntington’s Disease that may shape the future of drug development for the disease.  A team of researchers from the university found that a unique type of signalling found in damaged DNA signals huntingtin – a harmful mutant protein found in the genes of those diagnosed with Huntington’s Disease – to aid in DNA repair is defective for those with the condition.  The new hypothesis was published in the Proceedings of the National Academy of Science (PNAS).  Laura Bowie, a PhD student in the Department of Biochemistry and Biomedical Sciences at McMaster, says, “The concept was that if we applied the signalling molecule back in excess, even orally, this signalling can be restored in the Huntington’s disease mouse brain. The net result was that we fixed the modification of huntingtin not seen in mutant huntingtin in Huntington’s disease.”  Using this hypothesis, the study team discovered a molecule called N6-furfuryladenine, derived from the repair of DNA damage, which corrected the defect seen in mutant huntingtin.  “Based on dosing by different ways of this molecule in mouse Huntington’s disease models, Huntington’s disease symptoms were reversed,” says Bowie. “The mutant huntingtin protein levels were also restored to normal, which was a surprise to us.”  Ray Truant, senior author on the study, has dedicated his career to Huntington’s disease research and how mutation leads to Huntington’s disease. It was his lab that was the first to demonstrate that normal huntingtin was involved in DNA repair.  Truant argues that the traditional and controversial amyloid/protein misfolding hypothesis, where a group of proteins stick together forming brain deposits, is likely the result of the disease, rather than its cause.  He also stated that he considers this paper the most significant of his career, and that “This is an important new lead and a new hypothesis, but it is important for people to know this is not a drug or cure. This is the first new hypothesis for Huntington’s disease in 25 years that does not rely on the version of the amyloid hypothesis which has consistently failed in drug development for other diseases.”  Huntington’s Disease is an inherited, neurodegenerative illness that comes with dire physical, cognitive and emotional symptoms that often hit around middle age. The mutant huntingtin protein causes certain parts of the brain to die – specifically the caudate, the putamen and, as the disease progresses, the cerebral cortex.  Bev Heim-Myers, CEO of the Huntington Society of Canada adds “Innovative research initiatives, such as the work led by the team in Dr. Truant’s lab, including PhD student Laurie Bowie, has the potential to transform HD research. The answers we find for Huntington’s disease will likely lead to better understanding of treatments for other neurological diseases and it is important that we continue this cross-talk amongst neurodegenerative diseases.”  The study was conducted in partnership with the University of Alberta, Western University, Johns Hopkins University, and a collaboration with a U.S. biotech firm, Mitokinin LLC. Their work now continues in developing better derivatives of N6-furfuryladenine towards developing a drug.  This study was funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Huntington Society of Canada.  +++++  Vancouver-based Replicel Life Sciences announces that they have signed definitive agreements with YOFOTO, a Chinese company, solidifying their partnership to commercialise three of Replicel’s programs in Greater China.    The collaboration focuses on the development and commercialization in Greater China of RepliCel’s tendon regeneration cell therapy (RCT-01), skin rejuvenation cell therapy (RCS-01), and its injection technology in development for dermal applications (RCI-02) (excluding hair-related treatments).  YOFOTO Chairman states, “YOFOTO is a fast-growing company built on values related to beauty and healthy, active lifestyles. As a key part of developing and commercializing products related to these core values for our consumers, we are committed to being a leader in China in the commercialization of regenerative medicines.  The RepliCel cell therapy and injection technologies focused on skin rejuvenation and tendon repair are important building blocks in YOFOTO’s strategic healthcare vision. We are pleased to have structured a deal with RepliCel which results in YOFOTO not only being a development partner and commercial licensee but also an investor committed to contributing to RepliCel’s global success.”  YOFOTO’s investment in Replicel will include milestone payments, minimum program funding commitments, and sales royalties in exchange for an exclusive 15-year license to three of RepliCel products for Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Additionally, YOFOTO commits to spending a minimum of C$7 million on Replicel’s programs and associated cell processing manufacturing facility over the next five years in Greater China.  RepliCel president & CEO, Lee Buckler says, “In 2017 RepliCel delivered successful phase I data in all three of its cell therapy programs and functioning prototypes of its next-generation dermal injector,” says “We were committed to delivering a landmark partnership to RepliCel shareholders in 2018. The partnership with YOFOTO represents such a deal and provides RepliCel with not only an outstanding partner in Greater China but capital to move our programs forward in Europe and North America,” he adds.  The deposit of over $5 million has been paid by YOFOTO, but remains in escrow following the closing of the transaction. Once YOFOTO has met certain conditions and once relevant Chinese patents are issued in China, they will be assigned a YOFOTO-owned Canadian subsidiary.  This is very exciting news for Replicel and Canada alike, as Canadian biotech companies begin to spread across the Pacific, with more foreign companies seeking to invest in Canadian innovation and research.  +++++  An international team of scientists discovers a technique that predicts healthy individuals who are at risk of developing acute myeloid leukemia (AML), which is an aggressive and often deadly form of blood cancer.  The findings, published in Nature, illuminate the ‘black box of leukemia’ and answer the question of where, when and how the disease begins, says co-principal investigator Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre, University Health Network.  Dr. Dick, who is a professor, Department of Molecular Genetics, University of Toronto, holds the Canada Research Chair in Stem Cell Biology, and is co-leader of the Acute Leukemia Translational Research Initiative at the Ontario Institute for Cancer Research, says, “We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to acute myeloid leukemia. We can find these traces up to 10 years before acute myeloid leukemia actually develops. This long-time window gives us the first opportunity to think about how to prevent acute myeloid leukemia.”  Study author Dr. Sagi Abelson, a post-doctoral fellow in the Dick lab, says: “acute myeloid leukemia is a devastating disease diagnosed too late, with a 90 per cent mortality rate after the age of 65. Our findings show it is possible to identify individuals in the general population who are at high risk of developing acute myeloid leukemia through a genetic test on a blood sample. The ultimate goal is to identify these individuals and study how we can target the mutated blood cells long before the disease actually begins.”  The study stems from Dr. Dick’s 2014 discovery that a pre-leukemic stem cell could be found hiding amongst all the leukemia cells that are present in the blood sample taken when a person is first diagnosed with acute myeloid leukemia. The pre-leukemic stem cell still functions normally but it has taken the first step in generating pathway of cells that became more and more abnormal resulting in acute myeloid leukemia (Nature, February 12, 2014).  Dr. Dick says, “Our 2014 study predicted that people with early mutations in their blood stem cells, long before the disease appears and makes them sick, should be able to be detected within the general population by testing a blood sample for the presence of the mutation.”  The team extracted the data from more than 100 participants who developed acute myeloid leukemia six to 10 years after joining the study, plus the data from an age-matched cohort of more than 400 who did not develop the disease.  Dick adds, “We wanted to know if there was any difference between these two groups in the genetics of their ‘normal’ blood samples taken at enrollment. To find out, we developed a gene sequencing tool that captured the most common genes that get altered in acute myeloid leukemia and sequenced all the 500 blood samples.”  The gene sequencing tool was a success and picked up mutations years before an individual was diagnosed with acute myeloid leukemia to accurately predict those at risk. Moreover, the team used advanced computational technology to assay the information obtained from routinely collected blood tests taken over 15 years in Israel and housed in a massive database of 3.4 million electronic health records.  The study has linked acute myeloid leukemia with a common feature of aging called ARCH-age related clonal hematopoiesis, whereby blood stem cells acquire mutations and become a little more proliferative. The majority of people that have ARCH will not develop acute myeloid leukemia. It is a requirement to have acute myeloid leukemia, but not the other way around.  +++++  Machine learning is augmenting human ability and drastically changing possibilities. It is restructuring businesses and rewiring brains for transformative thinking. Whether it be to develop vaccines for deadly diseases or combat climate change, Canada is at the forefront of this monumental shift.  Canada has been on the vanguard of machine learning long before it became a popular headline. The growth and brilliant minds from around the country have led the way for Canada to place its mark with AI on the world and build a more promising ecosystem for the future.  Across the country, there have been several companies lending a hand in this newer and multi-faceted industry that will reshape history. Among those, innovative researchers are developing imaging devices for skin cancer, diagnostic platforms that analyse natural speech to detect dementia and mental decline, advanced signal analysis to diagnose coronary artery disease, just to name a few, and numerous others that stem to topics unrelated to health care, but keep Canada at the forefront of change.  This year Canada had its 31st Canadian Conference in Artificial Intelligence that stands to show how long Canada has been involved with this game-changing technology. Events like this bring together hundreds of leaders in research, industry, and government that provide a melting pot of inquisitive and like-minded people.  Life sciences is an industry that is filled with innovation and offers much economic promise for governments who desire to grow a knowledge-based economy. Therefore, Biotechnology Focus, in support of Global Biotech Week, is conducting a survey to gauge Canada’s innovation culture. The results will be featured in a special report in the September issue.  The report will highlight trends, identify areas of strengths that can be leveraged as well as opportunities for improvement to support growth for the Canadian life sciences industry.  Artificial intelligence and deep learning have the potential to revolutionize healthcare, and with Canada as a global frontrunner, we can expect to see exponential shifts in the upcoming years to come.  Add your voice to the survey at https://www.surveymonkey.com/r/BioFocus2018.   ++++++  Well, that wraps up another episode of Biotechnology Focus radio! Thanks for tuning in! And let’s remember that with Canada in the limelight it is important for everybody in the life sciences industry to make their voice heard, so please fill out the quick innovation survey so we can continue to enhance this spectacular industry and elevate health care. Until next time, from my desk to yours – this is Michelle Currie.  

    This week we have some encouraging findings on Alzheimer’s as researchers hunt for a cure, there were two research studies released from the University of Toronto: one involving aneurysms, and the other discussing ‘invisible’ pain, as well as, a recent discovery that could change the face of opioid manufacturing. Keep listening to hear all the details!  +++++  The population of the world is steadily living longer, increasing the likelihood of one in three developing a form of Alzheimer’s in their lifetime. Much work has been done to combat this debilitating disease, but as of yet, there is no cure. After a decade of work a team led by Hôpital Maisonneuve-Rosemont researcher and Université de Montréal associate professor Dr. Gilbert Bernier has shed promising light on the origin of the most common and prevalent form of Alzheimer’s hoping to someday help mitigate or even reverse the progress of the disease.  There are genetic variables when it comes to being diagnosed with this disease, but age is the principal risk factor. Many researchers are trying to better understand the genetic and pathophysiological risks, but few studies have focused on the origin of Alzheimer’s and its relationship with the aging of the brain.  Working from the idea that the most prevalent form of Alzheimer’s disease is not genetic but instead epigenetic, Dr. Bernier and his team carried out an extensive scientific investigation to better understand the role of a specific gene, BMI1, in the onset and development of the disease.  In a study published in 2009, researchers found that, in mice models, the mutation of the BMI1 gene triggered an accelerated and pathological aging of the brain and eyes. Based on this finding, Dr. Bernier’s team deduced that if the BMI1 gene stopped functioning in a human, it would also cause accelerated aging of the brain and the development of conditions related to Alzheimer’s disease.  By comparing the brains of deceased Alzheimer’s patients (taken from samples in the Douglas Bell Canada Brain Bank) with those of deceased non-Alzheimer’s patients of the same age, the team observed a marked decrease of the BMI1 gene only in patients who died of the disease. To verify that this decrease was not simply a consequence of the disease, the researchers repeated the process with patients who died of early onset Alzheimer’s disease, which is a genetic and much rarer form of the that strikes before the age of 50 and sometimes even before 40. The researchers discovered that there was no change in BMI1 gene expression in these cases.  In a third step, the team examined the brains of individuals who died from other aging-related dementias, and once again observed no change in BMI1 gene expression. Finally, using a complex method, the researchers recreated in the laboratory, neurons found in Alzheimer’s disease patients and healthy individuals. Once again, BMI1 gene expression only decreased in neurons of Alzheimer’s-disease patients.  The team concluded that the loss of BMI1 gene expression in the brains and neurons of patients with the common form of Alzheimer’s was not a consequence of the disease and could, therefore, be the cause.  This led to the researchers wanting to test their hypothesis that the loss of BMI1 plays a direct role in the development of Alzheimer’s disease. To do so, they created healthy human neurons in the lab. Once the neurons reached maturity, they deactivated the BMI1 gene using a genetic method. The results were remarkable. All the neuropathological markers of Alzheimer’s were reproduced in the lab, concluding to the researchers that the loss of BMI1 function in human neurons was enough to activate the disease.  Encouraged by their unexpected findings, the researchers also ran molecular studies to understand how the loss of BMI1 triggers the disease. These studies revealed that the loss of BMI1 causes an increase in production of beta-amyloid and tau proteins and a decrease in the neurons’ natural capacity to eliminate toxic proteins.  The researchers believe that the restoration of BMI1 gene expression in the neurons of Alzheimer’s disease patients in the preliminary stages could mitigate or even reverse the progress of the disease. This provides hope for the future to patients that are ravaged by this disease and for their caregivers alike.  +++++  Researchers from the University of Toronto’s Faculty of Applied Science & Engineering have found a way to bring together music, art, and science to provide better ways to stimulate and understand medical imaging of aneurysms in the brain.  Currently, if a patient comes into a medical clinic with an unruptured brain aneurysm, a clinician’s decision to operate or leave it depends on risk factors related to the patient’s medical history, as well as the aneurysm’s shape, size and location in the brain.  Aneurysms in the back of the brain, for example, are more likely to rupture than those at the front. However, many large aneurysms don’t ever rupture, and many small aneurysms that are normally left alone, do rupture.  So, the question remains, how to researchers treat riskier aneurysms?  David Steinman, a professor of mechanical engineering at UofT, uses an approach that fuses biomedical engineering and the arts to discover a solution to this issue. Collaborating with Toronto Western Hospital’s Aneurysm Clinic, as well as Peter Coppin, an assistant professor in the Faculty of Design at OCAD University, his lab is taking fresh insights from visual artists and sound designers to improve visual and audio communication in medical imaging, starting with aneurysms.  Using graphics and sound to amplify key features, while suppressing irrelevant information, would allow a user to visually concentrate on one field, while listening to the other. Certain aspects of complexity can be heard better than it can be seen.  This would then allow a clinician to more easily and efficiently decide whether to operate on an aneurysm.  If the simulated blood flow of the aneurysm were to show a very strong and unstable ‘jet’ coming into the aneurysm and against the aneurysm wall that might be a hint that that wall is more likely to be aggravated.  Steinmann hopes this innovative approach can help reduce the number of unnecessary treatments and the number of accidental ruptures.   To work alongside Coppin’s team at OCAD University, he has recruited post-doctoral researcher Thangam Natarajan to translate CFD visually, and master’s student Dan MacDonald to translate CFD into sounds. They are both in the department of mechanical and industrial engineering.  Steinman is optimistic that his work will lead to a consistent, new way of representing and understanding how to treat aneurysms in medical clinics.  +++++  Have you ever known anyone who has severe anxiety and feels like they are having a heart attack? A study at the University of Toronto has uncovered that the ‘invisible’ pain someone feels could actually be linked to the frontal lobe and pain transmission to the spine.  For 20 years, Min Zhuo, a professor of physiology, Faculty of Medicine, University of Toronto, has been enticed by chronic invisible pain with no obvious cause – no inflammation, no injury – and understanding how to treat it.  Zhuo used his suspicions about the frontal lobe in mice and rat models to prove that treating this area could be effective at preventing chronic pain. The results were published in Nature Communication.  Zhou explains, “When doctors can’t see anything wrong to cause chronic pain, often they think patients are making it up. But pain that originates in the frontal lobe would be very different from pain that comes from a physical injury, like a herniated disc. There wouldn’t necessarily be any injury to see. That’s because our personality and emotions live in this region. If the frontal lobe can produce physical pain, that pain would be deeply tied to emotions like anxiety.”  Scientists already knew that the prefrontal cortex was in some way involved in pain because it would light up in scans of people in pain. But that activity was always thought to be a symptom not cause.  When someone has extreme anxiety, more neurotransmitters are released that end up causing pain in the spine. This flood of neurotransmitters sends the spine into hyperdrive, and it starts treating ordinary sensations like pain. This could explain why anxiety can cause chest pain and make an individual think they are having a heart attack, or why some people experience pain when you touch them.   On the bright side, pain from the frontal lobe seems to be transmitted in a simple, direct way to the spine – making it relatively easy to shut down. Neurons in the frontal cortex send signals all the way down the spinal cord, whereas pain signals from other areas of the brain are mediated by a complex network.  In animals, Zhuo found that pain was associated with increased neurotransmitters released from the frontal cortex. He was able to lessen pain by reducing the amount released. His next step is to test this process in people.  This research will likely benefit those who suffer from anxiety coupled with neuropathic pain by using a painkiller that targets the frontal lobe.  The research was supported by the National Key Basic Science Research Project and the Natural Science Foundation of China.  +++++  Considering the many issues at the moment with opioid misuse, a biotechnology company from Calgary has found a way to mitigate some of the problems associated with manufacturing strong painkillers by using sugar instead of field grown opium poppies.   Epimeron Inc. has taken a major step toward that goal with its discovery of the isolation of a novel gene from the opium poppy (Papaver somniferum). The gene encodes the enzyme thebaine synthase, which had previously been hypothesized, but never found, until now. Thebaine is the essential starting point in the synthesis of widely-prescribed pharmaceuticals, including the analgesics oxycodone and hydrocodone and the addiction treatments buprenorphine and naltrexone.  Dr. John Wilson, director, Physical and Life Sciences, Innovate Calgary says, “The discovery of the thebaine synthase gene is significant. This work has unlocked the path to transforming the commercial production of opiates and indicates the very real potential of developing non-addictive opioids. It is satisfying to witness how Dr. Faccini’s comprehensive research has transitioned into creating a considerable impact.”  The breakthrough enables the completion of commercial, non-plant based biosynthetic manufacturing systems for active opioid agents and intermediates. It also opens the door to the creation of new opioid molecules, some with new characteristics such as reduced addictiveness. The discovery was published in a Nature Chemical Biology article titled “A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis“.  Peter Facchini, PhD, chief scientific officer of Epimeron comments that their demonstrated expertise in research and entrepreneurship will continue to drive this important endeavour. That they have made great progress so far, and this announcement is an indication of the potential that lies ahead in developing new drugs to manage pain.  Microbial production of active pharmaceutical ingredients from sugar as source material could potentially replace current opioid manufacturing methods that rely on opium poppies for raw ingredients. Current regulatory requirements and commercial practices require the importation of crushed poppy straw from producer countries such as India and Turkey. The imported ingredients are then processed locally to the final pharmaceutical products. Legal opium poppy farming in producer countries is plagued by diversion of legitimately made controlled substances into the illicit drug trade.  Local biosynthetic manufacturing directly from sugar will eliminate the need for opium poppy raw materials and will decrease or eliminate diversion as a source of illicit ingredients. Moving away from outmoded plant ingredient purification techniques also enables improved quality and consistency, simplified logistics compared to moving narcotic raw materials around the world and avoids using fertile land that could better be employed for food production.  In addition, the microbial manufacturing strains will provide a basis from which to develop novel less addictive opioids not currently accessible from the plant or traditional chemistries. Until now it was not commercially viable to attempt to make certain modifications to the opioid molecule, but microbial biosynthesis now makes them possible. From these, numerous candidate pharmaceuticals will arise for testing, and some of these may well be superior to currently marketed products.  +++++  Well that wraps up another episode of Biotechnology Focus radio! Thanks for listening in! Check out the articles in full at biotechnologyfocus.ca. Hope you all have a great week ahead! From my desk to yours – this is Michelle Currie.    

  Welcome back to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. So, as many of you know, we are coming up to a very busy and exciting time of the year, as BIO is just around the corner! And this isn’t just any regular BIO, this year marks the 25th anniversary in its inaugural location – Boston. It’s four days chalked full of keynotes, receptions and networking opportunities that will leave you trying to catch your breath at the end of the week. But if that doesn’t take your breath away, perhaps the performance by Diana Ross might at the largest BIO event of the year!  But bringing the focus back to Canada, a lot has been going on in the last few weeks that is worth mentioning. Keep listening to find out!  +++++  In a world where artificial intelligence has begun to incorporate itself in everything from life sciences to cars, it should come as no surprise that South Korean tech giant, Samsung, is jumping in with both feet opening AI Centres around the globe, one of which just opened in Canada’s most bustling city – Toronto.  The opening of the Toronto AI Centre comes on the heels of the company’s global announcement of two additional and newly established AI Centres in Cambridge, UK and Moscow, Russia as part of a new venture to tap into and contribute to the booming AI industry. The Toronto Centre will work in partnership with the company’s Silicon Valley team to pioneer AI research and development for the region.  Toronto has a rich history of innovation and discovery and is an ideal location for a vast amount of companies to call home. With access to key talent, Toronto is an idyllic place for research and development for speech recognition, where machine-learning technology was applied many years before it was widely applied to other fields. The vision is that the Samsung AI Centre will now serve a significant role in the advancement of AI with a focus on language understanding and computer vision technologies that will ultimately reduce the friction between the user and the device/service, whether it be mobile phones, TVs, appliances, or cars.  Located in Toronto’s downtown core at MaRS Discovery District, the new Samsung AI Centre is a part of a network of research Centres dedicated to research and development in the field of AI. The Centre is the second Samsung AI Centre to be established in North America, with the other in Mountain View, California. The North America AI Centres are led by senior vice president, Dr. Larry Heck, a renowned expert in machine learning for spoken and text language processing, who also co-leads the expansion of Samsung’s AI Centres around the globe.  The Toronto centre will be led by Dr. Sven Dickinson, newly appointed as the head of the Toronto lab, professor on leave and past chair of the Department of Computer Science at the University of Toronto. Dickinson is an expert in computer vision technologies, especially in the field of object recognition. He will play an integral part in Samsung’s research of core AI technologies that entail language, vision and other multi-modal interactions.  As one of the world’s largest urban innovation hubs, MaRS Discovery district supports promising innovators and ventures tackling key challenges in the sectors of cleantech, finance & commerce, and work & learning. In addition, and importantly, the vast MaRS community fosters cross-disciplinary collaboration which drives breakthrough discoveries and new solution for global audiences.  This announcement compliments earlier 2018 news of plans to launch additional AI centres in North America. Dr. Darin Graham will lead the opening of new labs in Canada as the head of Samsung’s Canadian AI Operations. Graham also helped create the Vector Institute – the renowned Canadian AI research institute, as a member of the founding team. The opening of AI centres in Canada will allow Samsung to expand its outpost for industry collaboration and talent recruitment in the major AI hubs in North America.  To date, Samsung has had remarkable success in leveraging Canada’s unique R&D talents for global impact. The Company’s Vancouver-based R&D centre has contributed to many in-market innovations and more than doubled its workforce, since opening with over 100 employees. With the addition of the AI centre in Toronto, the company plans to increase the R&D in Canada from current 100 to 200 in the near future. Additional developments and talent in Canada have been recognized through Samsung Electronics Canada subsidiaries, AdGear Technologies Inc. in Montreal and SigMast Communications Inc. in Halifax, Nova Scotia.  +++++  When it comes to what drugs get funded, how do provinces and the Canadian health care system decide which drugs to fund and which drugs not to? A team of University of Alberta researchers found that when a jury is made up of a cross-section of society and given proper information and context, people are willing to fund drugs and treatments for costly ultra-rare diseases, even at the expense of treatments for larger populations.  An example would be a rare genetic disorder that robs men of sight by the age of 40. It affects one person in 50,000 and does not yet have a cure. But it does have a very expensive, unproven gene therapy that holds the promise of delaying the inevitable.  Tania Stafinski, a researcher in the University of Alberta’s School of Public Health and director of the Health Technology and Policy Unity says, “The fallacy is that these kinds of decisions are based on the greatest good for the greatest number. It’s partly greatest need, partly what the gain looks like, partly the severity of the disease and partly the population affected. It is an interaction of all these things, but not whether it is utilitarian.”  To better understand the social values around spending on new technologies and commercially undeveloped “orphan drugs, Stafinski convened a pair of citizen juries that roughly matched the sociodemographic profile of people in and around Edmonton.  Just like in a legal setting, Stafinski called witnesses that represented government, health-care providers and patients, and led the juries through different trade-off exercises and scenarios. For the most part, specific drugs and technologies were avoided to rid the study of any bias and allow jurors to focus more on the characteristics of the people and what could be achieved.  The jury was put through seven trade-off exercises focusing on things that might matter to them, such as cost, the condition of the patient, what kind of technology is involved, how much improvement could be expected, and even caregiver burden.  Despite the stakes, uncertainties around whether the technology would be able to fully deliver on its claims didn’t play a significant role in decision-making. Even in cases, such as the gene therapy for vision disorder, where there was a risk the technology would fail, Stafinski found that jurors valued the information and innovation component of the research.  Final decisions on what technologies and drugs to fund are currently made by a provincial review committee, guided by a pan-Canadian evidence review process that leaves it up to the provinces to take into account social and ethical implications.  She says there are examples in the Canadian health-care system where a small gain for hundreds of thousands of people is implicitly sacrificed to give sufficient medical gains to a small group. One example is administering the flu vaccine—inhaled versus injected.  Stafinski explains that although a large segment of society may prefer to have the inhaled version of the flu vaccine, with a few exceptions, policy-makers aren’t spending the extra money for the inhaled vaccination, choosing instead to fund medications such as those that improve the quality of life for the 4,000 Canadians who suffer from cystic fibrosis.  +++++  A new study from The Ottawa Hospital is the first of its kind. The study suggests that treatment for erectile dysfunction coupled with a flu vaccine might be the solution to eradicating cancer cells after surgery. The study, published in OncoImmunology, shows that this unconventional strategy can reduce the spread of cancer by more than 90 percent in a mouse model. It is now being evaluated in a world-first clinical trial.  Senior author Dr. Rebecca Auer, surgical oncologist and head of cancer research at The Ottawa Hospital and associate professor at the University of Ottawa says, “Surgery is very effective in removing solid tumours. However, we’re now realizing that, tragically, surgery can also suppress the immune system in a way that makes it easier for any remaining cancer cells to persist and spread to other organs. Our research suggests that combining erectile dysfunction drugs with the flu vaccine may be able to block this phenomenon and help prevent cancer from coming back after surgery.”  The current study investigated sildenafil (Viagra), tadalafil (Cialis) and an inactivated influenza vaccine (Agriflu) in a mouse model that mimics the spread of cancer (metastasis) after surgery. The researchers evaluated these treatments by counting the number of metastases in mouse lungs. They found an average of:  37 metastases with cancer cells alone  129 metastases with cancer cells and surgery  24 metastases with cancer cells, surgery and one of the erectile dysfunction drugs  11 metastases with cancer cells, surgery, one of the erectile dysfunction drugs and the flu vaccine  Dr. Auer is now leading the first clinical trial in the world of an erectile dysfunction drug (tadalafil) and the flu vaccine in people with cancer. It will involve 24 patients at The Ottawa Hospital undergoing abdominal cancer surgery. This trial is designed to evaluate safety and look for changes in the immune system. If successful, larger trials could look at possible benefits to patients.  The researchers are excited about this research because it suggests that two safe and relatively inexpensive therapies may be able to solve a big problem in cancer. If confirmed in clinical trials, this could become the first therapy to address the immune problems caused by cancer surgery.  Using a variety of mouse and human models, Dr. Auer’s team has also made progress in understanding how erectile dysfunction drugs and the flu vaccine affect cancer after surgery. Normally, immune cells called natural killer (NK) cells play a significant role in killing metastatic cancer cells. But surgery causes another kind of immune cell, called a myeloid derived suppressor cell (MDSC), to block the NK cells. Dr. Auer’s team has found that erectile dysfunction drugs block these MDSCs, which allows the NK cells to do their job fighting cancer. The flu vaccine further stimulates the NK cells.  Dr. Auer stresses that although erectile dysfunction drugs and the flu vaccine are widely available, people with cancer should not self-medicate. Any changes in medication should be discussed with an oncologist.  +++++  Some of the hottest areas in biotech that are emerging and driving growth and investment are in the field of regenerative medicine and cell and gene therapy. There have been several acquisitions over the past year that really got the ball rolling with hopes to advance immunotherapies. Despite the curative potential, these therapies come with a hefty price tag and complex challenges. With the first immunotherapies to win regulatory approval in the United States, CCRM, a leader in developing and commercializing cell and gene therapies and regenerative medicine technologies, hosted a panel to discuss how we can bring these therapies to Canada.  The panel represented a wealth of knowledge covering regulatory and hands on approaches to the subject. It was moderated by Michael May, president and CEO of CCRM, and consisted of Donna Wall, MD, section head, Blood and Marrow Transplant/Cell Therapy Program, The Hospital for Sick Children (SickKids); Justin Shakespeare, executive director, Oncology Business Unit, Amgen; Patrick Bedford, senior manager, Clinical Translation and Regulatory Affairs, CCRM; and Aaron Dulgar-Tulloch, PhD, director of Bridge, GE Healthcare Cell Therapy.  There have been many decades of work in people trying variations of immunotherapy approaches and not getting a clinical signal. It was after researchers figured out T-cell biology and that they needed to bring not only the patients’ T-cells right up against the tumour cell but also that they had to get the T-cell excited and activated to go into cell division.  Donna Wall explains, “The first successful patient was only about six years ago. No question that the treatment can cure, as long as you take six years as to how long to treat a number of patients who otherwise have untreatable leukemia. That’s the first type of patients that we have when we have a new treatment. We take the patients where we have nothing else to offer. A number of patients do not make it to the treatment because it takes a while to engineer the cells; a number of patients may not have a response to the treatment; and a number of them who go into remission may end up relapsing. But for the first time, there are many who are responding positively to treatment and are not showing signs of leukemia.”  This is still in a very early-stage as of yet. It is not a one-and-done type of treatment. In order for this to work, the most common CAR-T product removes the cancer cells as well as the patient’s B-cells lifelong – giving them an immune deficiency. It is complex and comes with its own set of issues that may put up to 40 per cent of patients into intensive care for side effects of the CAR-T treatment. The treatment should not be taken lightly and will not be handed out over the counter.  The cost of the treatment is another factor entirely. Like anything new, cost is initially high but is expected to come down over time. It is a huge cost for a company to invest in and build the infrastructure that needs to be actualised as well as looking at regulatory costs. If the treatment becomes more mainstream, its costs pose another issue, as the health care system has not been designed to handle a large influx of big-ticket cases.  Patrick Bedford, CCRM, states, “There’s value in when you want to pay for something, but can you actually pay for it today is the real question. The number of drugs over $50,000 since a decade ago has gone from two to 20, and the drugs targeting orphan or rare diseases has all skyrocketed. There might not be a lot of people in each of these disease populations, but there are a lot of disease populations. So, the idea of affordability is really important. There are some new discussions right now about how to pay for these, like money back, or paying for performance type things, or rather than paying it all at once, pay three, four years later. There are a lot of ideas right now about how to afford the population if we choose they are worth the value to pay for.”  These are living drugs and therapeutics that have a very complex process on the manufacturing side as well as the rest of the supply chain. Each treatment batch is tailored to the patient. Many treatments start as autologous, but there are groups that are currently working on making this into more of an allogeneic process.  Aaron Dulgar-Tulloch explains, “Everyone wants to go from autologous to an allogeneic model. Every commercial entity would prefer to be in that allogeneic scenario because it is much better realised, there’s simplification in the supply chain, logistics, and the scale of benefits. We’re already starting to see groups trying to turn autologous into an allogeneic process. I think we will see more groups coming in with successful approaches to a more allogeneic or classical model.”  However, the playing field is changing as more treatments are reaching approval on a shorter timeline and with less clinical data. Even though much of that data presented to the regulators have been enormously successful, it is not typically a fast-moving field. This leaves the regulators to navigate through the treatments and do so in a receptive and responsible manner.  Since these therapies are still so new right now, it has put a particular strain, even on a global scale, to find individuals with expertise in scale up and industrial manufacturing coupled with biological cellular experience.  Dulgar-Tulloch explains that Canada in particular is feeling the pain from that, in that they don’t have a lot of the manufacturing infrastructure in Canada to pull from, and what Canada has is still heavily engaged in the bioprocess space.   CCRM has a centre devoted to improving the cell manufacturing process and is attracting international attention from companies who are looking for CCRM and GE’s expertise in process development. This work also feeds into the Good Manufacturing Process (GMP) facility that CCRM is building that provides space for therapeutics companies to run phase I and II clinical trials.  What it all boils down to when it comes to markets like Canada, is that timing is often regulatory-driven and balancing considerations as to where manufacturing is and how to support the local market, with timing as an implication on the pricing perspective. Canada needs to leverage its strengths on the clinical side so that we extract value from manufacturing and ultimately deliver these products to patients for commercialization.  +++++  Well that wraps up another episode of Biotechnology Focus radio! As always, we have all the stories online and in full to fish through at your leisure at biotechnologyfocus.ca. If you have a story idea or wish to make a comment, please email me at press@promotivemedia.ca. But until the next time, enjoy the spring weather and for those attending the BIO International Convention this year, good luck and enjoy! From my desk to yours – this is Michelle Currie.     

087 | Shifting thoughts and actions     Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. This week sheds light on antibacterial resistance and how that will change the course of the world on a widespread scale if our patterns do not change, how pharmacogenomics has become a new era in precision health, and how there may be a link between poor muscle health and type 1 diabetes.   Listen on to find out more!  ++++++  Ever consider a world where surgery was no longer an option? It is the unfortunate truth that if society does not slow the progression rate of antimicrobial resistance, life as we have come to know it will no longer be our future.  Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. Without such means of effective treatment, it will compromise therapies that have been used for decades in healthcare and puts society in a very precarious position. Treatments such as major surgery or chemotherapy may fade into the background.  As we stand on the precipice of a post-antibiotic apocalypse, this global concern has researchers all over the world clamouring to find a solution before this issue gets out of hand. Kevin Schwartz, an infection prevention and control and antimicrobial stewardship physician from Public Health Ontario is one of those researchers seeking a strategy.  Dr. Kevin Schwartz says, “Antimicrobial resistance is going to be one of the biggest future challenges and it really threatens the way that we practice medicine. We take for granted some of the modern advances of technology that we will really jeopardize if the trend of antimicrobial resistance continues.”  Antimicrobial resistance happens when microorganisms change from exposure to antimicrobial drugs. It is a natural process that happens over time, but, unfortunately, that timeline has been accelerated due to the misuse and overuse of antibiotics in people and animals. Whether it stems from prescribing patients’ antibiotics for things such as a cold or flu, or when they are given as growth promoters in animals or used to prevent disease in healthy animals, the truth is that we need to find a solution to contend with these “superbugs” – and fast.  Antimicrobial resistant-microbes are found in people, animals, food, and the environment (water, soil, and air.) They can transfer from person to person, from person to animal and animal to person – that includes food of an animal origin – and is present in every country worldwide.  It’s such a huge global overwhelming problem. From hospital settings to non-hospital settings, using more antibiotics than we probably need to. There are a variety of reasons for that. Antibiotics are effective and life-saving, and often patients present with unclear diagnoses so antibiotics are often used to be on the safe side and so we are not missing a potentially treatable illness.  Schwartz adds that the fields of antimicrobial stewardship are trying to develop ways to help physicians and prescribers use the antibiotics more appropriately. There’s probably depending on the study and the area being treated, inappropriately prescribed 30-50 per cent of the time. So, there is lots of room to improve our antibiotic use.   However, there isn’t one strategy that is applicable across all patient settings and types of conditions and there is a lot of variability as to how antimicrobial stewardship can be implemented. For instance, the approach to improving antibiotics is going to be quite different depending on the setting. Some examples would be the difference in the intensive care unit compared to hospitalized patients, compared to patients treated in the emergency room, compared to patients treated in family doctor offices.  Schwartz focus is mainly on the out-patient setting. So, how can we approach family physicians and community prescribers to use antibiotics more appropriately? Some of the strategies to do this would be to provide feedback to family physicians. Some of the stuff that they are scaling up to do is to be able to give doctors some comparisons and feedback. For example, how much antibiotics are they prescribing compared to their peers? Then by identifying those doctors that are high prescribers we can have a significant impact to decrease overall prescribing.  He goes on to suggest that there are other simple measures that can be implemented, such as a study done in the US that monitored how a poster mailed to family doctor clinics and signed by the corresponding physician with the intent to use antibiotics appropriately displayed in the waiting room affected overall usage. The study showed that even this simple measure decreased over-prescribing by 20 per cent.  Public Health Ontario have done something similar in Ontario over the last year, partnering with Choosing Wisely Canada, an organization aimed to decrease waste and improve healthcare efficiency. So, they sent the poster to about 13,000 doctors in Ontario to hang in their offices for a similar purpose.  There are discrepancies in the system across the country, however, about the amount of antibiotics being prescribed by population and contrasting health regions. This could be due to the variance of the practice of physicians in different geographical locations. Some prescribe more, while others tend to prescribe less – allocating education and feedback as one of the best means to observe overprescribing.  There are notable differences between urban and rural environments prescription and usage, but through multi-variable modelling incorporating these variables as predictors, it is still undetermined why some prescribe more over others.  Schwartz says, “We want to make sure people are using the appropriate medicine for the appropriate condition. So, we’re not using overly broad, overly toxic medication when we do not need to.”  A study that was done in the UK highlighted what would happen if the course of action did not change over time. They estimated that there are roughly 700,000 deaths a year from antibiotic-resistant infections and that if we do not do anything by the year 2050, that number could reach a high of 10,000,000. To put that number in another light, the death toll will surpass cancer and motor accidents combined.  By weight, most antibiotics are used in animals, not in humans, and there’s lots of antibiotics in the environment and in other parts of the population. So, there’s all these different approaches where we need to combine – animal veterinary health with human health with environment – and all these different things need to come together so that we can mitigate antibiotic exposure and an element of resistance.  The importance of this issue can not be understated. All the advances that have been accomplished in health care will be for naught if antimicrobial resistance continues down this path. Successfully taking care of premature babies, organ transplant, bone marrow transplant, and complex cancer therapies are all prime examples of procedures that will become incredibly difficult or impossible to achieve. They all rely on the fact that we can treat the complications that go hand in hand with the procedure – namely infections. These patients are more susceptible to bacterial infection, and without effective antibiotics the procedure may be too risky.  If you think back to the way things were during WWI when there was no antibiotics when even a small wound in battle could be life-threatening or limb-threatening. We really take for granted what we now consider a simple condition, where in the past was life-threatening. Schwartz says they will become life-threatening again in the absence of effective antibiotics for these problems.  Physicians and dentists are examples of prescribers that need to prescribe antibiotics appropriately, and for the public to have an awareness of the risks of taking antibiotics unnecessarily over time. This awareness needs to be spread before the world turns into a post-antibiotic era. Antimicrobial resistance is an inevitable process. The bacteria are alive, and they will evolve to survive.  ++++++  Genomics is driving a paradigm shift from a disease-oriented health-care system to one that is more precise, personalized, predictive, preventative and cost effective.  Advancements in technology are helping make genomics more affordable and accessible than ever before. Likewise, societal attitudes toward genomics in clinical care are shifting. We are no longer asking ‘if’ genomics should be integrated with clinical care. Instead we are asking ‘when’ and ‘how’ we can use genomics to benefit as many people as possible.  With a vision to advance the use and application of genomics in clinical practice, Genome BC has invested almost $370 million in over 160 research projects. Genomics research is already saving lives and improving health outcomes and disease management for patients touched by cancer, heart disease, autism, epilepsy, rare diseases and other debilitating diseases. As genomics research moves from the bench to the bedside, clinical applications of genomics will affect many areas of medicine over the next 10-20 years, improving disease prevention, diagnosis, and treatment, as well as informing our approaches to wellness, nutrition, and public health.  Genome BC has had a long-standing interest in, and support for, a particular aspect of precision health called pharmacogenomics. Since 2004 we have invested in a number of projects analyzing the unintended side effects of medication, known as adverse drug reactions (ADRs). The discipline of pharmacogenomics, identifying gene variants that predispose people to serious side effects of medications or that alter the way your body will respond to, or metabolize, certain drugs, is being applied to improve the safety and efficacy of many therapeutics and treatments. We are funding teams across different levels of research in this critical field: in the hospital alongside clinicians, in the pharmacy and with primary care physicians.  At the hospital level Dr. Bruce Carleton and his team are working to prevent ADRs by developing laboratory tests to predict the likelihood of a childhood cancer patient developing an ADR and tools to incorporate these tests into clinical practice. At the pharmacy level another group, led by Dr. Corey Nislow and the BC Pharmacy Association, has developed a community pharmacist-based approach to pharmacogenomic testing wherein a patient’s saliva is tested for genes that will predict adverse reactions to commonly prescribed drugs. Finally, at the family physician level Dr. Martin Dawes and his multi-disciplinary team of doctors, pharmacists, and epidemiologists have developed TreatGx, a unique medication decision support system. Using the highest levels of evidence, TreatGX identifies personalized medication options for multiple common conditions. The options are presented to the doctor in an easy-to-read format with helpful information such as dosing instructions, potential adverse reactions, and medication cost comparisons.  Each of these research teams are bringing new understanding to the table, as well as integrating their work for maximum benefit to patients.  The goal of pharmacogenomics is to improve patient outcomes. In order to implement this tool effectively we must:  Validate the efficacy of genomics applications in day-to-day patient care  Ensure we are increasing value to patients and lowering costs  Identify and provide information related to diagnostic criteria and provide the relevant pharmacogenomics test(s)  Develop guidelines to help clinicians use these tests  Change perceptions for healthcare professionals and patients  Genome BC is working closely with the provincial government, universities, clinicians and other stakeholders to advance the clinical use of pharmacogenomics.  Canada is not the only country working to implement precision health- there is a global effort working towards a common goal. Momentum is building and there are success stories of clinical implementation of genomics happening in real time around the world. In BC there has been a critical change in the Hereditary Cancer Screening Program at the BC Cancer Agency because of a gene panel test that enables clinicians to test for more than a dozen of the most common mutations all at once, rather than one-by-one. This test enables people to learn what cancers they may develop, how often to have medical follow-ups, what cancer screening to get and whether there are preventive lifestyle factors that might mitigate the risks. Wait times for this test have gone from several months to a few weeks and BC Cancer is even helping other provinces clear their backlog. The hereditary cancer panel is now being reimbursed by the BC provincial government and has been fully integrated in clinical practice.  Clinical practice has begun to incorporate genomics technology and applications. Ultimately physicians will have practice guidelines to best move patients along a treatment pathway that is best suited to their own genetic makeup.  +++++  A recent study coming out of the labs of McMaster and York Universities have found that there may be a link between poor muscle health and type 1 diabetes – even among the youth.  The research team analyzed muscle biopsies of young adults with and without Type 1 diabetes who exceed Diabetes Canada’s recommended weekly levels for physical activity.  The researchers found structural and functional changes in the power generation parts of the cell, or mitochondria, of those with diabetes. Not only were the mitochondria less capable of producing energy for the muscle, they were also releasing excessive amounts of toxic reactive oxygen species, related to cell damage.  These changes have the ability to affect metabolism – the chemical processes that occur within a living organism in order to maintain life – resulting in a greater difficulty controlling blood glucose, and if unmanaged, could accelerate to a disability. The study findings add poor muscle health to the list of better-known complications of Type 1 diabetes, including nerve damage, heart disease and kidney disorders.  Thomas Hawke, corresponding author of the study and a professor of pathology and molecular medicine at McMaster says, “Now we know that even active people with diabetes have changes in their muscles that could impair their ability to manage blood sugar. Knowing in the long term that this could contribute to faster development of disability, we can start to address it early on.”   Skeletal muscle is the largest metabolic organ and is the primary tissue for clearing blood sugar after eating a meal, so it is necessary to keep muscle as healthy as possible.  With regular aerobic exercise, mitochondria in muscle increase to therefore help muscle cells use more glucose and become more efficient.  The researchers believe these dysfunctional mitochondria are what’s causing the muscle to not use glucose properly and to also damage muscle cells in the process and were surprised to see the muscles were this unhealthy in young adults with Type 1 diabetes who were regularly active.  Researchers say while further study is needed, revising evidence-based exercise guidelines, specific for those with Type 1 diabetes, may be required to keep them in the best health.  ++++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for checking in! If you would like to read the stories in full, please visit our website at biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.    

086 | Paving the way of the future      Welcome to another episode of Biotechnology Focus radio! This week Toronto got their socks knocked off by an announcement from Sanofi; a Chinese company expresses interest in some of Canada’s regenerative medicine technologies; the scope of clinical trials in Canada is divulged at the recent Clinical Trials Ontario conference; and Shana Kelley and her team from the University of Toronto use new technology to essentially ‘find a needle in a haystack’ when it comes to prostate cancer. Keep listening to hear the latest news of Canada’s biotech scene!  +++++  French company Sanofi announces one of their largest investments ever in a single building and knocks the socks off the Toronto life sciences community. Sanofi announces that they are investing €350 million (C$500 million) into their Toronto facility to significantly increase capacity to meet the growing demand for pediatric and booster vaccines and demonstrate their commitment to innovation and leadership in global health.  The announcement was held at Sanofi Pasteur’s Canadian headquarters in Toronto and was joined by the Honourable Navdeep Bains, Minister of Innovation, Science and Economic Development, and the Honourable Steven Del Duca, Minister of Economic Development and Growth.  Canada has a strong legacy in the research and development of vaccines. With this investment, Sanofi is renewing their longstanding commitment to making Canada central in the effort to protect and improve human health across the globe. Vaccines save three million lives every year and this new facility will be one step closer to a world where no one suffers or dies from a vaccine-preventable disease.  The new facility will allow Sanofi Pasteur, the vaccines global business unit of Sanofi, to meet the growing demand of five-component acellular pertussis (5-acP) antigen. The building itself is expected to be completed within three to four years, a year or two to get the quality management system up and running, and a year or two to do product development and testing. The site will be equipped to produce the antigens used in the diphtheria and tetanus vaccines.  Philippe Luscan, the executive vice president of Global Industrial Affairs, Sanofi says that this project is one of the most important investments for the Sanofi global industrial network. It demonstrates the continued commitment to manufacturing excellence and to better serving their vaccines portfolio to people all over the world.  ++++++  New opportunities are arising at every turn for the regenerative medicine community. Research is at the tip of the iceberg, but a company in British Columbia isn’t waiting for the ice to melt. RepliCel, a regenerative medicine company, has been developing autologous cell therapies to treat conditions linked to the deficit of healthy cells required for normal function and healing. Their cell therapies are designed to treat chronic tendinosis, UV-damaged or aged skin, and pattern baldness as an alternative method to surgery, pills, and chemicals.  Recently, YOFOTO, one of China’s largest health and wellness companies announced its intention to invest significant financial backing into the company to market RepliCel’s tendon repair and skin rejuvenation products –  and they are not the only one – Shiseido, another giant, has been developing RepliCel’s hair regeneration technology for the Asian market.  Last year hit significant milestones for the company with production of the first fully functioning prototypes of their next generation dermal injector that is optimal for the delivery of injectables into the skin. With patents already issued in the United States and in Europe, the functioning prototypes allow RepliCel to display the applications of the device with other potential partners as they move forward at finalising the mold for the commercial-ready devices.  Last year also saw new clinical data produced on all three biologics programs – thinning hair (androgenic alopecia), aging/sun-damaged skin, and chronic tendinopathy (Achilles Tendinosis). The phase 1 clinical data demonstrated overwhelming product safety and highly encouraging signals of product efficacy to regrow hair, rejuvenate skin, and regenerate tendon tissue.  In 2013, RepliCel executed a co-development and licensing agreement with Shiseido that covered all of Asia for their hair regeneration program. Now, with the potential for another deal emerging in Greater China, we have real opportunity to leverage these partnerships to be a leader in regenerative medicine platform across Asia.  According to Brad Loncar, who recently launched a China BioPharm Index Fund, following the success of his Cancer Immunotherapy Fund, the biotechnology and pharmaceutical sectors are headed for exponential growth in the next few years and cell therapies are a significant focus in Greater China where he believes they are “ahead of the curve”.  Indeed, last month, the Chinese government unveiled its Made In China 2025 industrial plan in which it laid out a strategy for revolutionizing the Chinese biopharmaceutical industry through major investments in the sector and its supporting infrastructure.  It is a very exciting time for RepliCel as they move forward with a CE mark for their device in Europe and their potential expansion in Asia, as well as refining their US strategy for the launch of their dermal injector. With fascinating development projects in queue and continuing to look for the right opportunities, there will be substantial progress that will come from this innovative regenerative medicine company in the near future.  ++++++  It would be too easy to say that the recent CTO 2018 Clinical Trials Conference was an immense success – but it was. A sold-out event with 400 people speaks for itself. It was held in Toronto at the Sheraton Centre Hotel over two days chalked full of intrinsic speakers and panels discussing clinical research, clinical trials, and patient engagement.  The first day brought wonderful opening remarks from the Honourable Reza Moridi, Minister of Research, Innovation and Science, and was followed by Brian Goldman as the morning’s keynote speaker.  Brian Goldman is an ER physician, author and radio broadcaster of CBC’s White Coat, Black Art but chose to direct his keynote towards clinical trials in the age of disruption. Disruptive innovation has become a powerful change in health care, amongst many other industries. He defined exactly what disruptive innovation was with recent examples and its potential implications in health care – clinical trials, big data, clinical research.  To kick off the first panel was Jason Field, president and CEO of Life Sciences Ontario as a moderator of the evolving clinical research environment. The panel facilitated discussion on how to adapt to changes and how patients, health care and the economy will be impacted now and in the future.  As the day progressed there were speakers touching on future strategies, why Canada has a health care system, the misalignment of evidentiary interests and clearing the path ahead. An engrossing one-on-one interview after lunch with Francis Plummer, professor of medicine and medical microbiology from the University of Manitoba about a lesson in preparedness and how his work with the Ebola vaccine was a prime example of pre-empting what may happen, so that when and if it does, society will have a cure or at least a way to face it.  Clinical trials simply do not happen without participants, so the second panel brought patients and caregivers of patients to the stage to share their stories and experiences. They brought to life what the health care community works for and to and their advice on helping others find and join a clinical trial was instrumental.  The second day did not disappoint. Robert Bell, Minister of Health and Long-Term Care gave the opening remarks and welcomed the keynote speaker Ken Getz, director of sponsored research programs and research associate professor from the Tufts Center for the Study of Drug Development. Coincidently, he was also the keynote speaker at the very first Clinical Trials Conference that CTO put on a few years back; allowing him to describe first-hand how much it had grown and the benefits and impact this conference has on the clinical trials environment. He examined the current global operating environment for clinical research and specific areas where patient engagement practices and initiatives are being implemented.  Patient engagement with clinical trials remains a hot topic and largely uncharted territory. The first panel explored these models of patient engagement to give a voice to patient perspectives, quality of life values, and treatment experiences so that the health care system can get access to the drugs patients need sooner and create more robust trials and outcomes.  Following that, Molly Shoichet, Ontario’s first Chief Scientist was the interviewee of the day and went into detail about Canada’s research strengths, her aspirations for Ontario and Canada, and the innovation economy.  The remaining panels covered current interests such as big data in healthcare to advance opportunity and mitigate privacy risks, and how to advance ways to streamline the conduct of clinical trials and make Ontario and Canada a better place to have them executed. They engaged the audience in fruitful discussions and answered many burning questions from the listeners.  The two days compressed a wealth of knowledge, aspirations, and innovative ideas for the future of clinical trials in Ontario and Canada and left guests with an eagerness to start down that road.  +++++  Researchers at the University of Toronto have developed an innovative technology to identify which patients might not respond to standard therapy for prostate cancer before it is delivered from a “liquid biopsy”.  Prostate cancer is the most common cancer in men (excluding non-melanoma skin cancers) and third leading cause of death in Canada, according to the Canadian Cancer Society 2017 statistics. While several viable treatment options for prostate cancer exist, many men affected with prostate cancer will not respond to first-line treatments.  Shana Kelley, a professor at the University of Toronto divulges that screening for drug resistance is key to improving treatment approaches for many cancers. It is important for patients not to be on a therapy that won’t help them and it’s also important for health-care systems to avoid, whenever possible, delivering ineffective treatments.  Creating an option for a “liquid biopsy” via a blood test instead of more invasive alternatives is a step in the right direction and will save time, money, and recuperation time.  Kelley, lead investigator on the study published in Nature Chemistry, explains how her team has advanced a completely new approach using magnetic nanoparticles with DNA capture probes on their surface that can target circulating tumour cells (CTCs) in blood samples to see if the cells contain biomarkers associated with drug resistance.  The team traps the individual magnetized cells in a microfluidic device built in the lab, isolating them from all the other cells in the sample and allowing them to perform highly sensitive analysis. The cells with the highest magnetic content will also have a high messenger RNA expression for the biomarker associated with drug resistance. This means that patients with high messenger RNA expression should be considered for other therapies because they won’t respond to the first-line treatment.  Being able to access the circulating tumour cells  CTC cells is critical in the fight against cancer, as they carry information from the primary tumour that will divulge the best form of treatment for the patient. They are, however, outnumbered by a billion-to-one by normal cells in a patient’s blood making catching them a very daunting task.  In 2016, Kelley and her team published a study in Nature Nanotechnology that first introduced the microfluidic device and how it could be used to trap and analyze circulating tumour cells CTCs. The current study builds on this work by further targeting a specific biomarker within the circulating tumour cells CTCs.  The blood samples analyzed were collected from a small cohort of patients undergoing treatment for metastatic prostate cancer. In 10 of the patients tested, circulating tumour cells CTCs were visualized but only four of the patients exhibited the biomarker associated with drug resistance. This finding demonstrates that the new method can provide both a circulating tumour cells  CTC count and an analysis of the clinically relevant biomarker.  “We are very excited because this is like finding a needle in a haystack,” says Kelley. “It paves the way for a straightforward and personalized screening tool that allows clinicians to see if a patient will respond to therapy or not. Our method is also rapid, accurate and inexpensive, which gives it real potential for clinical uptake.”  Further studies need to be conducted to ensure consistent findings. Kelley and her team would also like to take this technology and expand it to other forms of cancer and disease.  ++++++  Well that’s it for another episode of Biotechnology Focus radio! To read the stories in full check out our website at biotechnologyfocus.ca. Thank you for listening and have a great week ahead! From my desk to yours – this is Michelle Currie.        

085 | When it sounds more sci-fi than fact  Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what’s happening on the Canadian biotech scene! This week we have some revolutionary research happening at the Centre for Drug Research and Development that sounds more sci-fi than fact, a treatment that allows the patient to breathe life back in, therapy that fits like a glove, and an over-the-counter drug that may be able to ward off Alzheimer’s disease. Listen in to find out more!  +++++  Empirical observations over the past many decades have suggested that certain types of virus infections could lead to cancer regression.  However, the use of so-called oncolytic viruses (OV) with the intent to treat cancer had been met with skepticism.  Now, thanks to technological advancements in genetic engineering and virus manufacturing, oncolytic virotherapy has gained considerable attention and demonstrated significant, though perhaps limited, clinical successes.    The Centre for Drug Research and Development (CDRD) have been working on ways to potentiate the utility of oncolytic viruses for cancer therapy in the hope that one day these strategies may be able to eliminate, or at the very least significantly reduce the need for traditional cytotoxic chemotherapy. Reducing the use of toxic treatments that impair the patient’s immune system is expected to lead to better overall survival and quality of life for countless cancer patients.  Dr. Ismael Samudio, Head of Biologics at the Centre for Drug Research and Development, has been preoccupied on how best to translate oncolytic virus strategies to the clinic, and in particular how to make these viruses work better in combination with targeted agents regardless of whether they are small molecules or antibodies. As Samudio explains, “We are cognizant that such a thing as a magic bullet for cancer is unlikely to exist. Pre-empting that, our work on oncolytic viruses is really trying to find the tools that we could take to the clinic (small molecules, antibodies) to make these agents successful in more cancer patients.”  Oncolytic viruses are a very powerful way to combat cancer. They are mostly genetically engineered to specifically target and kill cancer cells, without having an adverse reaction to the patient. They are also known for inducing an immune response against the cells they infiltrate.  Currently, the Centre for Drug Research and Development is working with two distinct types of oncolytic viruses. One of them is the precursor of Maraba – a potent engineered virus currently in clinical trials. The Centre is not aiming to treat one particular type of cancer and hopes that their research will effectively work in multiple tumour types.  Tumour cells, in general, have defective antiviral responses, and that’s why oncolytic viruses preferentially infect them. Cancer cells do not like to stop making proteins. They’re constantly growing and constantly making proteins. Normal cells have mechanisms that stop uncontrolled growth and protein synthesis. Because those mechanisms are defective in cancer cells, viruses infect them and they don’t have a way to shut down the production of the virus, resulting in massive viral expression and death of the infected tumour cells. Some cancer cells are more sensitive than others to oncolytic viruses, and understanding how to improve the efficacy or these biological agents is paramount to their success in the clinic.  The Centre so far has seen successful infection in every single cancer line that they have tested. Some cancer cells, however, tend to be able to escape death induced by the oncolytic virus, and thus in collaboration with several researchers, the centre for drug research and development is developing strategies to increase infectivity and engagement of the immune system.  The Centre doesn’t expect that there’s going to be infection of normal tissue. Nonetheless, they remain focused on delivering the treatment to where it needs to go – the tumour. There is no reason if your heart is healthy, or your kidney or liver, to expose those organs to our chemo-biological interventions – whether small molecules or antibodies – and reduce the safety of the approach. They want to make sure that those interventions go to the tumour tissue.  The centre expects for some of these efforts to take at least ten years to reach the clinic. Drug development can be a very daunting process, and of course, scientists and clinicians want to make sure it passes all safety and efficacy standards. The centre for drug research and development is a unique organization that focuses on a number of therapeutic areas, including cancer, auto-immune diseases, infectious diseases, neurodegenerative diseases and neurobiology in general. The knowledge gained at the Centre through innovative approaches, outside-the-box thinking, and cross-pollination of disciplines will ultimately lead to life-saving therapies.  Oncolytic viruses are such an amazing tool. They can, directly and indirectly, inhibit cancer progression, and I expect them to eventually become a mainstay in cancer therapy.  +++++  There has been substantial research coming out of the woodworks from across the country in so many areas of health. But, when you are living with a disease and finally find that medication which makes you feel like yourself again, there is truly nothing like it.  This was the case for Jennifer Falkiner. She had been diagnosed with asthma in her thirties and that progressed over time to severe asthma. Even the simple things we all take for granted became difficult, and little joys such as going to the movies, or having a solid nights sleep were taken away from her.  It is only now participating in an innovative clinical trial for severe uncontrolled asthma with the use of Fasenra – a respiratory biologic – and the research of Dr. Mark Fitzgerald, primary researcher of the study, that her quality of life and her motivation has returned. “It has been a transformation,” Jennifer says.  In the beginning, she wasn’t aware that she even had asthma. Starting as just a respiratory infection, her doctor gave her antibiotics and a puffer, but the infection was persistent and happened again and again. It was only upon going to another doctor that she was informed that she had asthma.  Over the years, Jennifer was put on a slew of puffers and medications and yet she still could not stop coughing – making social life, family, and work scenarios trying, and arduous at times.  Jennifer told me, “When I was much younger, before the asthma hit, I used to go tobogganing with my children. Then, I had grandkids come along and I couldn’t do that – but now I can. I got on this drug trial and now nothing stops me.”  The CALIMA trial was one of three pivotal trials to reduce severe exacerbation requiring prednisone and has shown a 50 per cent reduction in patients who had the active treatment in lieu of the placebo. Fasenra is the only respiratory biologic that provides direct, rapid and near-complete depletion of blood eosinophils from the first dose.  Around the world, asthma affects 315 million people, including an estimated 3 million Canadians. Roughly 250,000 Canadians live with severe, uncontrolled asthma, which can have a debilitating impact on lung function and quality of life.  Many of the current medications also come with countless side effects, that may deter the people who need the medication from taking it at all. Prednisone, for example, has been known to affect sleeping patterns, weight gain, severe depression, bloody or tarry stools, slow wound healing, dizziness – just to name a few. Fasenra, on the other hand, has had minute reported adverse reactions and is taken every eight weeks after the initial three doses.  Dr. Mark Fitzgerald hopes that in the future there will be blood or sputum tests to better identify the treatment that will work for each individual. We’re at a very exciting stage because, hopefully, these drugs will not only be used in patients with severe disease but also can be used earlier in the patient’s history of asthma to maybe modify the trajectory and prevent the progression to more severe disease.  Fasenra has been approved by Health Canada and represents a significant milestone for severe eosinophilic asthma patients, finally offering a new treatment option to help manage their condition.  The change for Jennifer has been dramatic. Going from a place where walking in the heat, scents, and the constant fear of the inability to breathe depicted what she could and could not do with her life, to now swim, skate, kayak, and play with her grandkids – she has never looked back.  +++++  Researchers at Western University have developed custom-fit gloves to help control tremors in patients with Parkinson’s disease. Not only does this glove help give them some sense of normality again, but it gives them their independence back as well.  Parkinson’s disease is a long-term degenerative disorder of the central nervous system that tends to affect the motor system the most. The disease progresses slowly over time, and is best exemplified through constant shaking and rigidity. Eventually leading to difficulty walking, swallowing problems and other health conditions. Symptoms may vary from patient to patient.  Anybody with Parkinson’s that has tremors have them in their entire body, but it’s the ones in their fingers that really prevent them from performing the activities of daily living.  The problem with a lot of the devices that are currently on the market is that they restrict movement in general, which still makes the tasks at hand hard to do. In the worst-case scenario, it can even suppress movement at the level of the elbows or wrists that exacerbates the tremors in the fingers.  The design model of the glove uses a system of sensors that track voluntary movements and separates them from involuntary tremors. The gloves will then suppress the tremor to allow fluid motion of movement. The current prototype glove was created for the left hand of student Yue Zhou, who used 3D printing to design a custom fit.  The team is also working on improving the glove’s hardware to make it more practical to wear, including reducing the size of the glove’s controller and improving its battery system. Once these pieces are all in place, they hope to find commercial partners to bring the gloves to the market.  If effective, this could dramatically change the lives of people living with Parkinson’s disease, allowing them to do daily tasks many people take for granted.  +++++  As the general population of the world ages and as diseases like dementia and Alzheimer’s become ever more prevalent, the hunt is on to discover a way to slow their progression or stop it entirely.  A Vancouver-based research team led by Canada’s most cited neuroscientist, Dr. Patrick McGeer, is now suggesting based upon his empirical research, that if a daily regimen of non-prescription NSAID (nonsteroidal anti-inflammatory drug) ibuprofen was started early enough it can prevent the onset of Alzheimer’s disease.  This study spells out a simple solution to a vastly complicated neurocognitive impediment. According to the Alzheimer’s Disease International’s World Alzheimer Report 2016, the disease affects 47 million people worldwide, costs the healthcare system more than US$818 billion per year and is the fifth leading cause of death in people over the age of 65. With Canada currently sitting around 560,000 people – a figure expected to rise to 937,000 by 2031 – there is no time to waste.  Dr. McGeer, who is president and CEO of Vancouver-based Aurin Biotech, and his wife, Dr. Edith McGeer, are among the most cited neuroscientists in the world. Their laboratory is world-renowned for their 30 years of work in neuroinflammation and neurodegenerative diseases, particularly Alzheimer’s disease.  In 2016, McGeer and his team announced that they had created a simple saliva test that can diagnose Alzheimer’s disease as well as predict future onset. The test is based on measuring the concentration of the peptide amyloid beta protein 42 (Abeta42) secreted in saliva. In most individuals, the rate of Abeta42 production is almost very similar regardless of sex or age. However, if that rate of production is two to three times higher, those individuals are inclined to develop Alzheimer’s disease. That is because Abeta42 is a relatively insoluble material, and although it is made everywhere in the body, deposits of it occur only in the brain, causing neuroinflammation, which destroys neurons in the brains of people with Alzheimer’s disease.  Contrary to the belief that Abeta 42 is only produced in the brain, Dr. McGeer’s team demonstrated that the peptide is made in all organs of the body and is secreted in saliva from the submandibular gland. As a result, with as little as one teaspoon of saliva, it is possible to predict whether an individual is fated to develop Alzheimer’s disease. This provides the patient with the opportunity to begin taking early preventive measures, such as consuming over the counters like ibuprofen.  Dr. McGeer explains that what they’ve learned through their research is that people who are at risk of developing Alzheimer’s exhibit the same elevated Abeta 42 levels as people who already have it; moreover, they exhibit those elevated levels throughout their lifetime so, theoretically, they could get tested anytime. Knowing that the prevalence of clinical Alzheimer’s Disease commences at age 65, they recommend that people get tested ten years before, at age 55, when the onset of Alzheimer’s would typically begin. If they exhibit elevated Abeta 42levels then, that is the time to begin taking daily ibuprofen to ward off the disease.  Unfortunately, most clinical trials to date have focused on patients whose cognitive deficits are already mild to severe, and when the therapeutic opportunities in this late stage of the disease are minimal. Consequently, every therapeutic trial has failed to arrest the disease’s progression. Their discovery is a game changer. They now have a simple test that can indicate if a person is fated to develop Alzheimer’s disease long before it begins to develop. Individuals can prevent that from happening through a simple solution that requires no prescription or visit to a doctor. This is a true breakthrough since it points in a direction where AD can eventually be eliminated.  +++++  Well, that wraps up another episode of Biotechnology Focus radio! Thanks for listening! If you have any questions or comments, please reach out to us at press@promotivemedia.ca. Tune in next week! From my desk to yours – this is Michelle Currie.            

Welcome to another episode of Biotechnology Focus radio – I am your host Michelle Currie. This week I will share with you an interesting article that I came across and then we will move on to the foremost part of the episode with Vatche Bartekian, here to tell us about his upcoming conference.      It was a work in progress, but after eight long years neuroscientists at the University of Montreal discovered a molecular mechanism that helps make sense of how Lou Gehrig’s disease, or amyotrophic lateral sclerosis (ALS), works.  This discovery could lead to a valuable new treatment in the fight to cure this crippling disease.  Amyotrophic Lateral Sclerosis is a disease that gradually paralyzes people because the brain is no longer able to communicate with the muscles of the body that we are typically able to move at will. Over time, as the muscles of the body break down, someone living with ALS will lose the ability to walk, talk, eat, swallow, and eventually breathe.  While studies such as this do not immediately give rise to new treatments for people living with ALS, they do deepen our understanding of the disease. ALS is very complicated; many cellular functions get mis-regulated. This type of work provides important information for future drug targets and the development of biomarkers aimed at detecting the disease more rapidly and following its progression.  The research began eight years ago when Jade Emmanuelle Deshaies, a research associate in neurosciences at the u of m and her supervisor, associate professor of neurosciences Christine Vande Velde, started investigating what happens to various molecules when TDP-43, a protein that binds the ‘messengers’ in the cell known collectively as RNA and that is central to ALS pathology, is removed from the nucleus.  In molecular biology, genes encode RNA and the RNA then gets translated into proteins. There are many different versions of RNA, each encoding many different versions of a protein. TDP-43, for one, binds RNA and can change how it is spliced – in a sequence of ABCD, for example, or of ABCEFG – a process called alternative splicing. Another RNA binding protein is hnRNP A1, and it gets spliced into two variants, both regulated by TDP-43. This is important because TDP-43 is known to be a major component of non-living substances in the cell called cytoplasmic inclusions that are seen in over 97 per cent of ALS cases.  The data they have show that when TDP-43 is either not there at all, or is just absent from the nucleus, you can change the splicing pattern of hnRNP A1. The big picture is that there is a much more broad spectrum of RNA metabolism mis-regulation than what was previously thought. And with that, there is more understanding of what’s going wrong, and given this new knowledge, they can potentially develop a therapy that targets this mechanism.  There is also development that parallels this research in spinal muscular atrophy (SMA) – another motor neuron disease. Scientists know that hnRNP A1 plays a role in its progress, controlling the splicing of an important gene called SMN, survival motor neuron. Vande Velde and her team don’t yet know whether or not the new splice variant they discovered changes SMN levels or function, but they point to a new drug therapy announced last year for SMA that does target the splicing of SMN by hnRNP A1.  The most amount of ALS research is done in Quebec than any other province. As Deshaies sums it up, “Science is rarely straightforward. It often takes a winding road before leading to explanations and true understanding of what we observe.”  Well that wraps up another episode of Biotechnology Focus radio. I want to thank  Vatche Bartekian again for discussing his upcoming conference with us, and thank you all for listening! From my desk to yours – this is Michelle Currie.  

Welcome to another episode of Biotechnology Focus radio! I am your host, Michelle Currie, here to give you the rundown on Canada’s biotech scene. This week we have stories about a possible Ebola treatment, how there may be a link between an increase in cholinergic system activity and parkinson’s disease, CRISPR makes its move on RNA, and according to a u of t study, rheumatoid arthritis patients have a higher risk of earlier mortality. So, keep listening to hear what’s going on from coast to coast! +++++ In the wake of the 2014 Ebola outbreak, with more than 11,000 known deaths, researchers are attempting to come up with innovative ways to prevent and cure the disease. Due to the dire nature of the virus, it sheds light on the limitations of the medication currently in circulation. Now, University of Guelph researchers have shown that an innovative antibody delivery method could offer an effective way to prevent and treat Ebola infection. Their goal is to make an antibody-based therapy that can protect against all strains of Ebola, and potentially the Marburg virus as well. It would be used to stop the spread of the virus in outbreak situations. The researchers say monoclonal antibody therapies (mAbs) hold promise for the treatment of the Ebola virus, but monoclonal antibody therapies are a costly operation and provide only short-term immunity. That could change though thanks to a recent discovery by lead researchers Sarah Wootton and Laura van Lieshout. Their findings were published in the Journal of Infectious Diseases. The approach technique that the researchers are using has been seen in studies with the human immunodeficiency virus (HIV). It delivers a monoclonal antibody gene through a viral vector to bypass the need to generate a natural immune response – something that can take the body weeks to occur and quite frankly, time is of the essence with this particular disease. Wootton found that using the adeno-associated virus (AAV) to deliver antibodies was remarkably effective at keeping the Ebola virus infection at bay in mice. Other researchers have used the adeno-associated virus extensively to treat a variety of genetic disorders. The goal is to use the adeno-associated virus gene therapy vector to deliver the DNA blueprint to a cell, and that cell will produce a protective antibody against the Ebola virus, which is then secreted into the bloodstream and protects mice from infection. The approach provided 100 per cent protection against an Ebola infection in mice using two separate types of monoclonal antibodies, and 83 per cent protection with a third. A “cocktail” of two antibodies provided sustained protection against Ebola for up to five months. Once the antibody gene is delivered, antibodies will be continually reproduced in the bloodstream. Mice in the laboratory expressed the antibody for more than 300 days. Researchers are hoping to utilize this technology in a post-exposure scenario. +++++ There is a particular gene mutation that happens in the brain that could be linked to an inherited form of Parkinson’s disease (PD) that might shed some light on a controversial theory about where PD begins in the brain. Idiopathic PD, a sporadic form of the disease, affects the dopamine system and is treated with replacement therapy to restore the brain’s natural chemical balance and alleviate physical symptoms. Frequently, other neurotransmitter systems are involved, but it is not yet clear whether this happens pre- or post the dopamine loss characteristic. By studying people with the inherited form of the disease, researchers hope that they will be able to determine brain involvement prior to the development of symptoms. The results of an international collaboration, led by Dr. Jon Stoessl, published in The Lancet Neurology shows that mutations in the LRRK2 – a gene associated with an inherited form of PD – can cause imbalances in the cholinergic system of the brain, but not in the way they thought. The cholinergic system is responsible for learning and memory. An imbalanced cholinergic system has been witnessed in other neurodegenerative disorders, including Alzheimer’s. While the investigators expected to find evidence of reduced cholinergic activity in the brain, positron emission tomography (PET) scans revealed widespread increases not only in people with the LRRK2 mutation-related form of PD, but also in unaffected individuals who carry the mutation but do not yet have manifestations of disease. Changes in the cholinergic system are thought to contribute to PD complications including cognitive difficulties, postural instability and sleep disturbances. It is possible that an increase in activity may reflect the brain’s attempt to compensate for dysfunction related to the mutated gene, and may also explain why patients with LRRK2 mutations have fewer problems with certain complications of disease, even though their PD is in most ways similar to the usual sporadic form of the disease. This provides a tremendous opportunity to study people with Parkinson-causing genetic mutations before they develop. The findings of this study have considerable implications for understanding how the disease begins to manifest in the years before diagnosis, and builds on research previously published last year that demonstrated that patients with the LRRK2 mutation show an increase in serotonin nerve terminals before a formal Parkinson’s Disease diagnosis, possibly reflecting the brain’s attempts to compensate for the decrease in dopamine associated with onset of physical symptoms. According to Statistics Canada, PD is the second most common neurodegenerative disease in Canada with an estimated 55,000 people suffering from it. It is a progressive disorder of the nervous system that affects movement. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while a tremor may be the most well-known sign of Parkinson’s disease, the disorder also commonly causes stiffness or slowing of movement that worsens as it progresses. The majority of new diagnoses are in adults over the age of 64. +++++ CRISPR/Cas9, the “scissors” of life sciences, is now not only targeting DNA, but RNA as well. Scientists from the Salk Institute in the U.S. have created this new tool, CasRx, to correct protein imbalances in cells. This provides researchers with a powerful way to develop new gene therapies, as well as investigate fundamental biological functions. Bioengineers are like nature’s detectives, searching for clues in patterns of DNA to help solve the mysteries of genetic diseases. CRISPR has revolutionized genome engineering, and the researchers wanted to expand the toolbox from DNA to RNA. CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea (the domain of single-celled microorganisms). These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses and other foreign bodies. They do so primarily by chopping up and destroying the DNA of a foreign invader. When these components are transferred into other, more complex, organisms, it allows for the manipulation of genes, or “editing.” The Salk team decided to search bacterial genomes for new CRISPR enzymes that could target RNA, which could then be engineered to address problems with RNA and resulting proteins. A given RNA message, for example, can be expressed at varying levels and its balance relative to other RNAs is critical for healthy function. Furthermore, RNA can be spliced in various ways to make different proteins, but problems with splicing can lead to diseases such as spinal muscular atrophy, atypical cystic fibrosis and frontotemporal dementia (FTD). So, a drug that targets toxic RNAs or RNAs resulting from improper splicing could have a life-changing impact for people with these types of devastating diseases. The researchers began the project with the hypothesis that different CRISPR systems may have been specialized throughout an evolutionary arms race between bacteria and their viruses, potentially giving them the ability to target viral RNA. They developed a computational program to search bacterial DNA databases for particular repeating DNA sequences. Whilst this was happening, they discovered a family of CRISPR enzymes that targets RNA. They called it Cas13. The name is derived from the gut bacterium Ruminococcus flaveflacians XPD3002 due to it being the best version for use in human cells, because just like Cas9, Cas13 enzymes originate from different bacterial species and vary in activity. The scientists tried out this new method in a dementia patient, attempting to replace the damaged cells with healthy ones. CasRx was 80 per cent effective. The team genetically engineered CasRx to target RNA sequences for the version of the tau protein that is overabundant. They did this by packaging CasRx into a virus and delivering it to neurons grown from a frontotemporal degeneration patient’s stem cells. Compared to other technologies that target RNA, CasRx is unique due to its small size – making it easier to package into therapeutically relevant viral vectors – its high degree of effectiveness, and that it creates no discernible off-target effects compared to RNA interference. The Salk team is excited about the possibilities their tool opens up for exploring new biological questions about RNA and protein function, as well as therapies to tackle RNA and protein-based diseases. To quote one of the authors of the study, “Nature is full of so many secrets. It’s really a rich, untapped resource for inventing new technologies.” +++++ According to a study done by the University of Toronto, sufferers of rheumatoid arthritis are more likely to have further complications and die at a younger age than the general population. The study was examining causes of death of Ontarians over a 14-year period. Everyone deserves to live the same length and quality of life. Mortality is also one of the strongest markers to evaluate inadequate care. The excess mortality related to rheumatoid arthritis that the researchers observed may suggest inadequate attention to control of the disease and its related morbidity. The study is one of the largest of its kind to comprehensively look at causes of death over an extended period. More than 87,000 patients with rheumatoid arthritis in Ontario were included in the study and compared with more than 340,000 members of the general population over a span of 14 years. Causes of death were found to be quite similar between the general population and those with rheumatoid arthritis, but the notable difference was that those with the disease were dying at a much younger age – which is something that concerns the researchers. Rheumatoid arthritis is a chronic condition that can affect two to three per cent of older adults. As an inflammatory disease, rheumatoid arthritis can affect more than just the joints in the body – ongoing inflammation often leads to further complications and multimorbidity in patients. This means that individuals will likely have multiple chronic conditions occurring simultaneously, such as diabetes and high blood pressure, or heart disease and a respiratory illness. The study also found that among arthritis sufferers, one in three were dying of complications attributed to heart disease. The head researcher wants to underscore the importance of improving preventative measures to slow down the progression of some of these co-morbid conditions in order to improve a patients’ overall life expectancy. The hope through this research is that it will shed light and awareness on the disease and inspire patients to play a more active and vigilant role when it comes to their health. The study was published in Arthritis Care & Research and was supported by the Catherine and Fredrik Eaton Charitable Foundation, the Canadian Institutes of Health Research, and the Arthritis Society Post Doctoral Fellowship. +++++ Well, that wraps up another episode of Biotechnology Focus radio! I hope you enjoyed it! Next week I’ll have Vatche Bartekian on the show to tell me about his event coming up in May! Stay tuned and have a great week! From my desk to yours – this is Michelle Currie.

082 | Discoveries: contending with the superbugs  Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what’s happening on the Canadian biotech scene. This week there have been some novel research discoveries that McMaster University, The University of Alberta, The University of British Columbia, The University of Waterloo and The University of Manitoba have been pumping out that I would like to share with you. So, keep listening and find out what exciting stories are happening from coast to coast!   +++++  Researchers from McMaster University have pinpointed a gene that is the culprit for neurological disorders, including autism.  They found that modifications of the gene thousand and one amino-acid kinase 2, aka TAOK2, has a direct link to these disorders. This gene encodes a serine/threonine protein kinase that is involved in many different processes, including, cell signaling, microtubule organization and stability, and apoptosis. This is the first comprehensive study that supports previous research suggesting the involvement of this gene and is published in Molecular Psychiatry.  According to Karun Singh, study co-author and researcher with McMaster’s Stem Cell and Cancer Research Institute, “Our studies reveal that in complex brain disorders that have a loss of many genes, a single deleted gene is sufficient to cause symptoms for the patients. This is exciting because it focuses our research effort on the individual gene, saving time and money as it will speed up the development of targeted therapeutics to this gene alone.”  Many neurodevelopmental disorders are caused by large missing pieces of genetic material in a person’s genome that contain several genes, termed a ‘microdeletion’. Accurately diagnosing a gene microdeletion helps doctors to predict patient outcome and to determine if a new treatment is available.  The researchers used genetically engineered models and computer algorithms to study a human genome, which allowed them to pinpoint the single gene in question.  The next step will be to screen candidate drugs that correct the cognitive brain deficits cause by genetic mutations in TAOK2, and identify candidates for pilot clinical trials.  The paper complements a study led by Singh on gene microdeletion published in American Journal of Human Genetics in early February.  The research was led by Singh in collaboration with Stephen Scherer from the Hospital for Sick Children. Additional researchers came from McMaster University, the Hospital for Sick Children, University of Toronto, the University Medical Center Hamburg-Eppendorf in Germany, Assiut University in Egypt and the University of Helsinki in Finland.  +++++  There was a time when the thought of growing a human body part in a lab would have been outrageous. These days, those once incredulous thoughts have become a reality.  Now, the researchers from the University of Alberta have found a way to grow human nose cartilage that will be safer and more accessible to use for facial reconstruction surgeons and will mean fewer surgeries and less pain for patients.  The team conducting the research project used a clinically approved collagen biomaterial as a scaffold to grow new cartilage that they can harvest and shape for patients who need nasal reconstruction.  The vision is that the surgeon would simply take a small biopsy of cartilage from inside the nose and provide it to the lab. The lab would then manufacture the cartilage for the surgeon in the appropriate shape and size. Once it has finished growing, the surgeon would then take that cartilage and insert it into the patient’s nose at the time of the operation.  Nasal reconstruction is a relatively common surgical outcome resulting from skin cancer. In 2015, there were more than three million cases of skin cancer in North America alone. About one-third of cases occur on a patient’s nose, with treatment options often leading to loss of function and disfigurement.  This typically ends up being a very traumatic event for the patient and comes with a high pathological cost. They really can’t hide these defects – they are very obvious. Often these patients will not interact socially because they are embarrassed by their appearance. So, the ability to help reconstruct a patient’s nose is really important.  With the assistance of six cartilage donors, the researchers harvested the cartilage cells – known as nasal chondrocytes – and multiplied them in a lab. They then seeded the cells in a scaffold to grow new tissue in a bioreactor. It takes roughly six weeks to grow enough cartilage for nasal reconstruction.  This engineered cartilage minimizes other risks and is deemed to be a superior method than that of the cartilage harvesting from the rib or ear. Cartilage taken from the rib carries a greater chance of infection, potentially collapsing the lung and an unnecessary surgery that will take the patient a longer to recuperate. Rib cartilage can also undergo warping after nasal reconstruction surgery, meaning it may not maintain the shape the surgeon wants it to. Cartilage taken from the ear is also challenging in that it can become brittle and difficult for the surgeon to manipulate. Engineered cartilage eliminates those deficiencies and could potentially supply unlimited quantities for surgeons. The University of Alberta team says it can also be custom-made for the patient.  An associate professor of surgery at the University of Alberta describes it as kind of like when you go to the tailor to get your suit made. They measure the patient based on the digital scans, and then basically just populate the cells.  The researchers have yet to test their high-quality engineered nasal cartilage in human patients. They hope that within the next two years they can begin clinical trials to prove the efficacy of the cartilage in the operating room.  +++++    Recent research conducted by the University of British Columbia (UBC)and BC Cancer denotes that precancerous lesions in the mouths of non-smokers are more likely to evolve into cancer than smokers.  Even though smoking unequivocally is related to mouth cancers, UBC dentistry PhD candidate Leigha Rock found that precancerous lesions in non-smokers are more than twice as likely to progress to cancer at an even faster rate than a smoking-associated counterpart. The study was published in Oral Oncology.  This is the first published study where the main focus was to examine the difference in risk of progression to oral cancer between non-smokers and smokers with oral precancerous lesions. While other studies have also reported a higher rate of transformation among non-smokers, this study looked at multiple risk factors including genetic markers.  Rock and colleagues looked at the case history of 445 patients with oral epithelial dysplasia (OED), a type of precancerous oral lesion, enrolled in the B.C. Oral Cancer Prediction Longitudinal study. One-third of the patients were non-smokers.  Amongst the researchers’ findings were that lesions on the floor of the mouth in non-smokers were 38 times more likely to progress to cancer than in smokers. This study is the first to report a quicker progression to cancer in non-smokers indicated at three-year and five-year rates of progression, and at 7 and 6.5 per cent higher than smokers, respectively.  The researchers suggest that the main difference in outcomes is due to a variance in the root causes of the lesions. In smokers, the oral epithelial dysplasia OED is likely the result of environmental factors. Whereas, in non-smokers, genetic susceptibility or mutations are likely to blame.  The findings show that molecular genomic markers can identify high-risk lesions, regardless of risky habits like smoking, and should be an important consideration in patient management.  The study’s results also stress the importance of taking oral lesions seriously, especially when they occur in non-smokers: “If you see a lesion in a smoker, be worried. If you see a lesion in a non-smoker, be very worried. Don’t assume it can’t be cancer because they’re a non-smoker; research indicates non-smokers may be at higher risk.”  This research was funded by the BC Cancer Foundation, the National Institutes of Health, and the National Institute of Dental and Craniofacial Research.  +++++  And some very exciting news, especially in this age of antimicrobial resistance, scientists from the University of Waterloo and the University of Manitoba have developed a new therapy to combat deadly bacteria that infects patients worldwide.  The new therapy is a biocide that targets an antibiotic-defiant bacterium such as Methicillin-resistant strafill cock us  are e us  (Staphylococcus aureus) (MRSA) to combat superbugs.  Professors at the University of Waterloo wanted to be able to help vulnerable patients suffering from chronic infections. Because once a patient is infected with a resistant strain of bacteria it is very difficult to get them well again.  This latest development provides hope in an age where bacteria are becoming resistant to antibiotics faster than researchers can develop new ones. The World Health Organization estimates 700,000 people die annually from antibiotic-resistant infections and they expect this toll to climb to 10 million by 2050, higher than the current death rate from cancer and even motor accidents combined.   University of Manitoba researcher, Song Liu, created a potent biocide that kills all bacterial cells – even the antibiotic-resistant ones. The biocide was limited to surface wounds due to its poor selectivity between bacterial and mammalian cells, but if they could deliver the biocide to a target inside the body, it would kill even the most resistant superbug.  Accompanying Liu’s work, Ho encased the biocide in solid-lipid nanoparticles and then added an antibody – a protein that would seek out Methicillin-resistant strafill cock us are e us bacteria over other cells. When the solid-lipid nanoparticles reach the bacteria, they release the biocide, killing the target but leaving healthy cells unaffected. The optimal outcome.  The results from the initial experiments appear to be quite promising. Still, there is a lot of work to do before this is available as an alternative to antibiotics. The next step is to find out whether the biocide gets released outside or inside the cell according to the researchers.   The researchers also believe that antimicrobial resistance will be unlikely to happen with their solid-lipid nanoparticles because the antibodies that are being used to target Methicillin-resistant strafill cock us are e us won’t cause the bacteria to develop an enzyme or other defence mechanisms in response.  This therapy offers a new line of defence in this critical time to confidently outpace antibiotic resistance.  +++++  Well, that’s it for this week’s episode of Biotechnology Focus radio. Perhaps next week there will be more riveting news from these universities and more from others I am sure. Modern medicine is advancing at such a pace, it’s hard to keep up! Be sure to check our website for the full stories and get your fill daily of what's happening on the Canadian biotech scene at www.biotechnologyfocus.ca. Thanks so much for listening in! Hope you have a great week ahead. From my desk to yours – this is Michelle Currie.   

Welcome to another episode of Biotechnology Focus radio. I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene. This week I’ll be discussing how the regenerative medicine community is abuzz, expanding personalized medicine, and the very recent announcement from the Ontario government that brings great news to the life sciences sector.   +++++  The regenerative medicine field, which includes cell and gene therapies (CGTs), is still abuzz with the fall approvals of three CGTs by the U.S. Food and Drug Administration: Novartis’ Kymriah, Gilead/Kite Pharma’s Yescarta and Spark Therapeutics Inc.’s Luxturna.  At the Cell and Gene Therapy World conference in Miami, Florida (January 22-25), many of the talks were either about the approved treatments or congratulating the industry on these significant milestones.  Reni Benjamin, of Raymond James Financial, reminded delegates that the pharmaceutical industry is also feeling confident about cell and gene therapes s. Acquisitions in 2017 were worth billions: Gilead acquired Kite for $11.9 billion, Takeda bought Ariad for $5.2 billion and Roche acquired Ignyta for $1.7 billion. As the conference was just getting underway, the news was announced that Celgene is buying Juno Therapeutics for $9 billion.  Illustrating the future of the field are the more than 1,300 currently open clinical trials listing stem cells (from sources other than blood) as the primary therapeutic, the 1,000 clinical trials in gene therapy, and clinical trials involving chimeric antigen receptor (CAR) T cells (a type of immune system cell) accounted for around half of clinical trials in 20162.  As such, global investment in the cell and gene therapies and regenerative medicine industry is booming. For example, public and private investment in immuno-oncology has grown to $1.5 billion2. When it comes to gene therapies, the forecast for the year 2025 ranges from $4.3 billion to $10 billion2 due to recent advances in the understanding of genetic disease, and innovation in genetic engineering tools. Altogether, it is estimated that the regenerative medicine industry will explode to a valuation of up to $20 billion by the year 2025.     So, where does Canada sit in terms of being an innovator in these advanced therapeutic technologies?     Let’s start with the good news. Canada is a prominent force in this emerging global field. We have a strong backbone of Canada-based researchers who are recognized scientific leaders, and a robust system for the development of highly-qualified personnel through Canada’s universities. We have also benefited from strategic investments in research, collaborative networks and infrastructure, and are developing a deep understanding of how to translate these advanced therapies from the bench to the bedside.  One way to sustain Canada’s leadership position is to nurture the right skills and education within our borders. Encouraging STEM (science, technology, engineering and mathematics) education from a young age is a necessary first step. Extending STEM-based education with biomedical engineering programs at the university level is a good strategy for supporting the growth of Canada’s CGT and regenerative medicine industry. Biomedical engineering – where engineering design principles and mathematics are applied to medicine and biology, allowing students to make significant contributions to improving human health by finding new diagnostic or therapeutic solutions – is an area Canadian universities are increasingly focusing on.  An illustration of how biomedical engineers are already impacting the regenerative medicine field can be found at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) and at Medicine by Design. The 55-year-old IBBME fosters a multidisciplinary research community where students and investigators in engineering, medicine and dentistry collaborate to develop innovative solutions that address global challenges in human health. Their impact can be seen in the development of breakthrough biomedical devices and new biomaterial products.  Funded in 2015 with a generous federal grant, Medicine by Design builds on IBBME’s successful multidisciplinary model to conceive, create and test strategies to address critical problems in regenerative medicine. By working across disciplines and generating and using emerging methods, like genome editing, computational modelling and synthetic biology, Medicine by Design is generating a deeper understanding of core biological concepts controlling stem cell fate, and devising new therapeutic approaches that will improve health outcomes.  This successful approach is now receiving a significant boost in Vancouver, where the University of British Columbia (UBC) has launched a new School of Biomedical Engineering as a partnership between the Faculty of Medicine and the Faculty of Applied Science.     Centre of commercialization and regenerative medicine, a Toronto-based leader in developing and commercializing regenerative medicine technologies, understands how the intersection of engineering and medicine, introduced by biomedical engineers, can help provide the tools that will advance the industry now and into the future.  One area where Centre of commercialization and regenerative medicine employs biomedical engineers is in its Centre for Advanced Therapeutic Cell Technologies (CATCT), a joint investment by GE Healthcare and the Government of Canada. Biomedical engineers work on process development strategies and solutions, and on projects involving reprogramming and engineering cells, immunotherapies and gene therapies. Operational for over a year, Centre for Advanced Therapeutic Cell Technologies was created to accelerate the development and adoption of cell manufacturing technologies that improve patient access to novel regenerative medicine-based therapies. The team introduces new technologies to solve emerging technical challenges and closes gaps in current and future workflows.      Our next challenge is to make certain that we have the people, technologies, processes and infrastructure to ensure Canadians have equitable access to these potentially game-changing therapies. Biomedical engineering programs are a start. Engineers are trained to look for efficiencies through cost reductions and improved technologies.  We need to build a Canadian innovation cluster that will attract talent and business expertise to capture the intellectual property developed in Canada and mobilize it for the benefit of Canadians.  We also need to work with government to position our health-care system as part of our competitive advantage. A big part of getting to this step in getting to this solution is starting to look at health economic models that integrate therapeutic costs and savings from development through to long term patent treatment costs.  Together, Canada’s companies, networks, researchers, start-ups and innovative centres are starting to deliver on the promise of regenerative medicine. With the technical know-how and a spirit of collaboration, biomedical engineers are a driving force in the country’s quest to lead the regenerative medicine industry into the future.  +++++  Personalized medicine is becoming a very popular term heard amongst researchers and the scientific community. It is a more tailored approach to preventing disease that is based on an individual’s predispositions. Whichever way you put it – personalized medicine, genomic medicine, precision medicine – it is reshaping healthcare.  Dr. Richard Kim, a scientist at Lawson Health Research Institute and clinical pharmacologist at London Health Sciences Centre (LHSC), has received $4.4 million to study an expanded personalized medicine program at London Health Sciences Centre. One-third of the funding comes from the provincial government’s Ontario Research Fund (ORF) while the remainder is contributions from Thermo Fisher Scientific and donor funding through London Health Sciences Foundation.  Personalized medicine uses pharmacogenomics – the study of genetic changes that alter the way a person responds to individual drugs. The new funding will enable researchers to follow patient outcomes and assess the cost-effectiveness of London Health Sciences Centre’s personalized medicine program, providing evidence on the relationship between the cost of the program and how patient care is improved.  London Health Sciences Centre’s personalized medicine program involves the full integration of research into patient care and was the first in Canada to implement personalized medicine as a clinical strategy. The practice began in 2008 through Dr. Kim’s research on warfarin – a blood thinner prescribed to treat blood clots.  Adverse drug reactions in patients is a significant problem. Some drugs do not metabolize with every patient, and can even lead to toxicity. It is the fourth leading cause of death among hospitalized patients and costs the Canadian health care system over $5 billion a year.  Dr. Kim explains, “For every medication, there are patients who should be prescribed lower or higher than the recommended standard dose and patients who should be prescribed an entirely different medication. Personalized medicine studies a patient’s unique DNA to ensure he or she is prescribed the right dose of the right medication at the right time.”  The team’s research continues to grow since inception and is providing testing for several other drugs. For example, they can now offer testing for cancer patients that have been prescribed 5-fluorouracil – a highly toxic form of chemotherapy – but is integral in treating bowel, stomach, head, and neck cancers.  Oncologists at London Health Sciences Centre’s London Regional Cancer Program can now refer patients to get tested for their potential reaction to 5-fluorouracil to better predict if they may or may not have an adverse reaction. A blood sample will be taken and tested with genotyping, and a full report given to the recommending oncologist. If a patient’s predicted to react poorly with the drug, they can follow clinical guidelines to either reduce the dose or find a method of treatment.  The team will study the outcomes of any patients referred to the program, including hospital stays, emergency department visits, and physician visits. These patients will be compared to others in the province using provincial health care data from the Institute for Clinical Evaluative Sciences (ICES). The team hopes to demonstrate the cost-effectiveness of implementing personalized medicine in a large acute-care hospital in Ontario.  +++++  The most recent announcement from the government of Ontario this past week was that it is investing $50 million in venture capital funds focused on life sciences.  Ontario is moving forward with their plan for a venture capital fund to aid life sciences firms access the capital they need to grow their business, create jobs, and grow on a global level.  The Ontario Capital Growth Corporation (OCGC) would like to identify fund managers to partner with other institutional investors such as corporations, banks and pension funds. Ontario’s new life sciences venture capital fund is designed to respond to the challenges faced in raising capital by innovative, high-potential life sciences companies to scale up and reach global markets.  The Hon. Reza Moridi, Minister of Research and Innovation says, “Providing much needed capital to growing life sciences companies is a crucial step towards a strong and sustainable life sciences ecosystem. Supporting high-potential life sciences companies will create good jobs and help commercialize technologies and services for improved healthcare at home and around the world.”  Ontario’s new venture capital fund focused on life sciences is designed to respond to the challenges faced in raising capital by innovative, high-potential life sciences companies to scale up and reach global markets. It will also help businesses foster new discoveries, including new technologies, treatments and cures for illnesses while supporting high quality, knowledge-based jobs for people across the province. It will also drive Ontario’s ability to attract and retain talent.  The Ontario Capital Growth Corporation, venture capital agency of the government of Ontario, was created to promote and develop the venture capital sector in Ontario, so that more high-potential technology companies have access to the capital needed to grow and prosper.  Supporting innovation in the life sciences is part of Ontario’s plan to create fairness and opportunity during this period of rapid economic change. The plan includes a higher minimum wage and better working conditions, free tuition for hundreds of thousands of students, easier access to affordable child care, and free prescription drugs for everyone under 25 through the biggest expansion of medicare in a generation.  Ontario is the largest life sciences jurisdiction in Canada with more than 50 per cent of overall Canadian revenue. The province includes an incredible 1,840 firms employing close to 61,000 people across the province. This fund will open many doorways for Canadians and Ontarians.   +++++  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 press@promotivemedia.ca. To see the articles in full check out the website biotechnologyfocus.ca ca so you don’t miss a beat! Have a momentous week. From my desk to yours – this is Michelle Currie.

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 press@promotivemedia.ca. 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.      

079 | Acknowledging some of the industry’s best Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you the lowdown on the Canadian biotech scene. Today, I will be discussing such topics as empathic distress, the top industry leaders that stood out from the pack this past year, a plausible link between white matter in the brain and Alzheimer’s, and how a multi-use drug could benefit those combatting esophageal cancer. +++++ Ever felt like you were picking up someone’s stress just from being around them? As if their experiences radiated and permeated your own mind? Well, studies being done at the Hotchkiss Brain Institute in the Cumming School of Medicine at the University of Calgary are studying precisely that. Researchers have been told by healthcare workers that empathic nuances seem to transfer from soldiers’ who suffer from PTSD to their partners or family members, despite never having served in the military. Jaideep Bains, PhD, and his team at the Hotchkiss Brain Institute (HBI) in the Cumming School of Medicine have discovered that stress transmitted from others can change the brain in the same way as real stress does. The research team studied the effects of stress in pairs of male or female mice. They removed one mouse from each pair and exposed it to a mild stress before returning it to its partner. They then examined the responses of a specific population of brain cells in each mouse, which revealed that networks in the brains of both the stressed mouse and naïve partner were altered in the same way. “There has been other literature that shows stress can be transferred — and our study is actually showing the brain is changed by that transferred stress,” says Toni-Lee Sterley, a postdoctoral fellow in Bains’s lab and the study’s lead author. “The neurons that control the brain’s response to stress showed changes in unstressed partners that were identical to those we measured in the stressed mice.” The researchers discovered that the activation of the neurons causes the release of a chemical signal that acts as an “alarm pheromone” from the mouse that alerts the partner. The partner who detects the signal can then in turn, alert additional members of the group. Bains adds, “What we can begin to think about is whether other people’s experiences or stresses may be changing us in a way that we don’t fully understand. The study also demonstrates that traits we think of as uniquely human are evolutionary conserved biological traits.” The study demonstrates that the effects of stress on the brain are reversed only in female mice following a social interaction. The residual effects of stress on neurons in females were cut almost in half following time spent with unstressed partners. However, this did not apply or ring true for males. If some of the effects of stress are erased through social interactions, but this benefit is limited to females, this may provide insights into how we design personalized approaches for the treatment of stress disorders in people. +++++ I would also like to acknowledge this year’s Biotechnology Focus top life sciences CEO picks from across the country. They are industry leaders who have stood out from the pack, and whose tenacity is extremely admirable. They have captured the attention of the Canadian biotech investment community and are the cream of the crop as Chief Executive Officers on the Canadian biotech scene. With the help of some leading Canadian biotech analysts and investors, we’ve put together a list of who we think the Top 5 CEOs who elevate their companies are. The criteria for making the list: They are CEOs who have delivered in the past and are with companies where they have a chance of delivering in the future. They aren’t necessarily leading the biggest companies, but rather, they qualify because they are the best leaders. Dr. Clarissa Desjardins is a co-founder of Clementia Pharmaceuticals and has been the president since its inception in 2010 and chief executive officer since 2012. Her company is a clinical-stage biopharmaceutical company that develops disease-modifying treatments for patients suffering from debilitating bone and other diseases. Cameron Piron is an industry-recognized leader and innovator in image-guided surgery. Although he is not a CEO, he has made a profound impact as a co-founder and president at Synaptive Medical – a company that is breaking ground with advanced medical devices, medical imaging and information science. Their BrightMatter technology combines surgical planning and navigation, robotic digital microscopy and informatics to create a family of devices to obtain patient data and retrieve it when needed the most. Dr. Ali Tehrani is a co-founder, president and chief executive officer of Zymeworks Inc., and an obvious choice for this year’s list. He has been an integral part of the success of Zymeworks, which continues to partner and flourish at a dizzying rate. The company’s lead clinical candidate, ZW25, is a Azymetric bispecific antibody that targets two distinct domains of the HER2 receptor resulting in multiple differentiated mechanisms of action. Carl Hansen started AbCellera working out of his laboratory at the University of British Columbia in 2012. He is the president and CEO of this privately held biotech company that provides enabling technologies for the discovery and development of monoclonal (mAb) therapies directly from natural immune cells. AbCellera’s lead technology is a proprietary single cell antibody discovery platform that provides researchers the opportunity to rapidly identify mAb therapeutic candidates from the natural immune repertoires of any species. Lloyd Segal, a veteran biotech executive, president and CEO of Repare Therapeutics was another indisputable choice for this list. Lloyd is an entrepreneur-in-residence at Versant Ventures, and from 2010-2016 was a managing partner at Persistence Capital Partners, a leading healthcare private equity investor. He held CEO roles at Caprion Pharmaceuticals, which he co-founded, Advanced Bioconcept and Thallion Pharmaceuticals, and has served as a director of several public and private corporations in the U.S. and Canada. Repare is developing new, precision oncology drugs for patients that target specific vulnerabilities of tumour cells. Its approach assimilates insights from several fields of cell biology including DNA repair and synthetic lethality. There was no shortage of great candidates for this year’s top biotech CEO picks. After so many outstanding nominations, it was hard to narrow it down to just five. Here are some of the Honourable mentions who just missed the cut: Roberto Bellini – President and CEO of Bellus Health   Richard Glickman – Founder and CEO of Aurinia Pharmaceuticals Arun Menawat – CEO of Profound Medical Sammy Farah – President and CEO of Turnstone Biologics Anthony Cheung – President and CEO of enGene Inc. David Main – President and CEO of Aquinox Pharmaceuticals   +++++ Scientists from Sunnybrook Hospital in Toronto have discovered that the white matter found in the brain chips away at memory by shrinking the brain and contributing more to dementia than previously thought. White matter hyperintensities (WMH) are bright spots on MRI scans – tissue in the brain that is wearing away due to effects of aging and vascular risk factors on the brain’s small vessels. The research, published in the February 2018 issue of the journal Neurology, showed that individuals with extensive small vessel disease had profound shrinking of the temporal lobe, an important brain region that is instrumental to learning and memory function. The study included over 700 participants of the Sunnybrook Dementia Study led by Dr. Sandra E. Black. The researchers’ analyses showed that shrinkage of the temporal lobe explained how WMH were associated with memory problems. WMH is associated with poor verbal recall more so due to temporal lobe shrinkage and deficits in recognition memory – the most sensitive and specific cognitive sign of Alzheimer’s disease – in people with Alzheimer’s disease and across other late-life dementia syndromes including post-stroke dementia. The researchers stress that small vessel disease is often a “silent” contributor to cognitive decline and dementia, as do large vessel strokes. Since small vessels are linked to brain shrinkage and memory problems it is important to recognize vascular brain disease as a potential “root cause” for dementia. +++++ Faculty of Medicine scientists at the University of British Columbia have discovered that a drug currently being tested for autoimmune disorders of the blood may also be a knight in shining armour for those with esophageal cancer. Shane Duggan, a postdoctoral fellow in the division of gastroenterology, and Dermot Kelleher, dean of the faculty of medicine, found that fostamatinib reduced the growth rate of esophageal adenocarcinoma in mice by at least 70 per cent compared to the control growth. Esophageal cancer has abysmal survival rates (only 14 per cent alive five years after diagnosis) and is a growing Canadian health concern. The scientists published their discovery in Cellular and Molecular Gastroenterology and Hepatology explaining their search for possible treatment targets for esophageal cancer – the sixth-leading cause of cancer-related mortality and second-deadliest form of cancer. Duggan and Kelleher conducted a screen of about 6,000 genes found in a cell that are known or emerging drug targets in a variety of diseases. They found about 300 druggable genes specific to esophageal cancer and using biopsies of esophageal cancer from Br itish Columbia, the U.K., and Ireland, they narrowed that list to three primary candidates. It was then that they noticed something surprising – the genes were more associated with immune cells than with the epithelial cells of the esophagus. Esophageal cancer is often preceded by a condition called Barrett’s esophagus, which results from gastroesophagealreflux disease (GERD). The reflux causes the inflammation and induces the esophageal tissue to transform into intestinal-like tissue. The immune cells unleashed by GERD may never fully depart from the esophagus, causing low-level inflammation that continues undetected and without symptoms. The transformed esophageal epithelial cells, after prolonged exposure to inflammation, seem to produce and become driven by a protein called spleen tyrosine kinase (SYK). Duggan and Kelleher then turned their attention to fostamatinib, an SYK inhibitor developed by San Francisco-based Rigel Pharmaceuticals Inc., which has shown promise in immune and lymphoproliferative disorders. Proving them right, their study expressed that the drug was very effective at stopping the growth of esophageal cancer in vitro and in mice models that had been implanted with human esophageal cancer cells. While the tumours expanded rapidly in the mice in the control group, there was virtually no growth of the tumours in the mice given fostamatinib. +++++ Well that wraps up another episode! As always, if you have any questions or comments, I would love to hear from you, so feel free to email me at press@promotivemedia.ca. In the meantime, thanks for listening and hope you have a great week ahead! From my desk to yours – this is Michelle Currie.

Welcome to another episode of Biotechnology Focus radio. This week we are discussing a recent investment, the engineering of a CAR molecule to combat cancer, a new surgical treatment and a study notifying us that viruses are literally falling to Earth. I am your host Michelle Currie, here to bring you the lowdown on the Canadian biotech scene. +++++ Ontario Genomics is investing $100,000 in one of Toronto’s newest start-up companies, Bright Angel Therapeutics to develop anti-fungal treatments. Fungal diseases are a growing global public health problem. Data compiled by the Global Action Fund for Fungal Infections shows that “over 300 million people are afflicted with a serious fungal infection and 25 million are at high risk of dying or losing their sight.” Mortality due to fungal infections is primarily due to the development of resistance to the few available anti-fungal compounds. Ontario Genomics’ Pre-commercial Business Development Fund investment will help Bright Angel Therapeutics develop new compounds that are strategic to treating fungal infections. By targeting a stress response mechanism that enables fungi to become drug-resistant, this strategy will transform existing antifungals from ineffective to highly effective against all the leading fungal pathogens. Importantly, the stress response-targeting strategy being developed by Bright Angel enhances the efficacy of all three classes of current antifungal drugs. It is applicable to the leading causes of invasive fungal infection and prevents the emergence of drug-resistance. This strategy will allow the company to tap into the existing very large antifungal market. Bright Angel Therapeutics was erected by Drs. Leah Cowan and Luke Whitesell, now both at the University of Toronto, based on technology developed while they were at the Whitehead Institute in collaboration with the late Dr. Susan Lindquist. With the assistance of MaRS Innovation, the company has partnered with Schrödinger Inc. to take advantage of Schrödinger’s world class molecular modeling and drug design expertise and will continue to provide start-up guidance. +++++ The Princess Margaret Cancer Centre in Toronto is leading a research team spearheaded by senior scientist Dr. Naoto Hirano that may have engineered a molecule that has the potential to augment existing immunotherapies. This research is of relevance to chimeric antigen receptor (CAR) T-cell therapy – a therapy that uses a patient’s own immune cells (T-cells) identify and fight cancer cells. This study was published in the journal Nature Medicine. In layman’s terms, CAR T-cell therapies help the immune system to recognize and destroy cancer cells through a process that begins with the isolation of T-cells from patients. Next, these cells are genetically modified so that they produce the CAR molecule on their surface. The CAR molecule is a modified version of a T-cell receptor that is specifically engineered to recognize tumour cells. These genetically modified cells are then grown in a lab to increase their numbers before being infused back into patients. So far, CAR T-cell therapy has only been approved in the United States for blood cancers such as advanced lymphoma and acute lymphoblastic leukemia. This is believed to be because existing CAR constructs don’t produce certain signals known to support the continued destruction of malignant cells, despite alerting the immune system of the presence of cancer. Dr. Hirano’s team has engineered a molecule that activates specific protein signalling pathways which are known to enhance the growth and function of T-cells. Hirano comments, “In our experimental models, the CAR molecule we engineered enabled T-cells to display more potent activity against different cancers, including solid tumours, which remain a challenge in the field. Current CAR T-cell therapies have shown limited success when treating solid tumours likely because of the harsh conditions faced by immune cells attempting to infiltrate the interior of the tumour. Furthermore, in these same models, we did not observe any worsening of potential side effects.” While these findings are preliminary, the performance of the engineered CAR T-cells created by Hirano’s team suggests that optimizing CAR molecules may help to broaden the effectiveness of CAR T-cell therapies against different cancers. Work in the future will entail translating these findings into clinical trials to explore the safety and efficacy of the engineered CAR molecule. +++++ The Centre hospitalier de l’Université de Montréal (CHUM) is now offering a new surgical treatment for patients with lymphedema – swelling that is caused by the abnormal accumulation of lymph fluid in a body part, often the arms or legs. Lymphovenous bypass surgery consists of microsurgically connecting the affected lymphatic vessels to the venous system to facilitate lymph fluid flow, decrease the severity of the lymphedema, reduce the complications related to this chronic disease and improve the quality of life of lymphedema patients. The first lymphovenous bypass surgery to be performed at the CHUM took place on January 22, 2018, by Dr. Ali Izadpanah, on a 23-year-old man who developed secondary lymphedema following a motorcycle accident. For nearly three and a half years, Olivier Lagacé was limited in his movements because of the swelling in his left leg, which had nearly 35 per cent more volume than his right leg, despite continuous treatments (decongestive therapy and the wearing of compression socks). With the surgery performed at the CHUM, he will be able to hope for a reduction in not only the swelling in his leg, but in the number of treatments needed to control his illness. Lymphedema is a chronic disease for which there is currently no cure. Lymphovenous bypass surgery was developed in Japan a few years ago and, although it is now available at many centres in the U.S., it is still not easily accessible by Canadians with lymphedema. As a university hospital centre, the CHUM is presently working on developing a multidisciplinary clinical and research unit for lymphedema treatment that will make it possible not only to treat patients with this disease, but also to create a prospective database related to patients’ post-operative quality of life improvement. With its microsurgical simulation laboratory, which opened a year ago on the premises of the Direction de l’enseignement et de l’Académie CHUM, the hospital centre is also equipped and has set plans to contribute to lymphovenous surgery training and the development of new methods specific to this type of surgery. +++++ Although there are many things people would like to fall for – whether it be in love or for a joke – viruses are most likely not one of them. Researchers from Canada, Spain and the US have discovered that there are a phenomenal number of viruses circulating around the Earth’s atmosphere – and they’re falling back to the ground every day. This study marks the first-time scientists have quantified the viruses being swept up from the Earth’s surface into the free troposphere (layer of atmosphere beyond Earth’s weather systems but below the stratosphere where jet airplanes fly). The viruses can be carried thousands of kilometres there before descending back to the Earth’s surface. University of British Columbia virologist Curtis Suttle, one of the senior authors of a paper in the International Society for Microbial Ecology Journal that outlines the findings says, “Every day, more than 800 million viruses are deposited per square metre above the planetary boundary layer—that’s 25 viruses for each person in Canada.” This study brings to light how nearly identical viruses can traverse time and space and seemingly “pop up” around the globe. Suttle adds, “Roughly 20 years ago we began finding genetically similar viruses occurring in very different environments around the globe. This preponderance of long-residence viruses travelling the atmosphere likely explains why—it’s quite conceivable to have a virus swept up into the atmosphere on one continent and deposited on another.” Bacteria and viruses are swept up into the atmosphere mostly from natural methods like small particles in soil or dust and sea spray. Suttle and colleagues at the University of British Columbia, the University of Granada and San Diego State University wanted to know how much of that material is carried up above the atmospheric boundary layer above 2,500 to 3,000 metres. At that altitude, particles are subject to long-range transport unlike particles lower in the atmosphere. The researchers found that billions of viruses and millions of bacteria particles are falling to earth per square metre per day. They used the high altitude of Spain’s Sierra Nevada Mountains to calculate these findings with deposition rates for viruses being nine to 461 times greater than the rates of bacteria. Bacteria and viruses are typically deposited back to Earth via rain events and Saharan dust intrusions. However, the rain was less efficient removing viruses from the atmosphere. Hitching rides with smaller, lighter particles like sea spray, viruses have the ability to stay at loftier heights for longer and give themselves a farther reach. The findings are an eye-opener as to how pandemics and other viruses spread around the world. Now the problem remains – what will fall and when? +++++ Well that wraps up another episode of Biotechnology Focus radio. If you have any questions, comments or story ideas, please contact us at press@promotivemedia.ca, and don’t forget to follow us on our twitter handle @BiotechFocus. I also wanted to mention that The 2018 Clinical Trials Conference hosted by Clinical Trials Ontario are taking place March 27-28, 2018 at the Sheraton Hotel in Toronto. It is an interactive and collaborative 2-day event that brings together over 350 people from industry, research, ethics, healthcare, non-profit, government and academia to exchange ideas, build relationships, and develop new strategies with respect to improving clinical trials and bringing more clinical trials to Ontario. For information about speakers, session topics, and registration, visit www.ctoconference.ca. Hope you all have a great week! From my desk to yours – this is Michelle Currie.

Welcome to another episode of Biotechnology Focus radio. This week we are discussing some of the recent mergers and acquisitions that have been rocking the headlines, some recently awarded grants and how machines are moving fast. I am your host Michelle Currie, here to bring you the lowdown on the Canadian biotech scene.  +++++  Celgene, a biotech giant, has merged with and acquired Juno Therapeutics and their leading blockbuster drug cancer therapy in one of their largest deals ever. For a total of $9 billion, Celgene will pay $87 a share in cash for those not already owned by this corporation.  Celgene and Juno have been collaborating since June 2015 under which the two companies would leverage T cell therapeutic strategies to develop treatments for patients with cancer and autoimmune diseases with an initial focus on CAR-T and TCR technologies. In April 2016, Celgene exercised its option to develop and commercialize the Juno CD19 program outside of North America and China.  Juno develops cell-based cancer immunotherapies based on chimeric antigen receptor and high-affinity T cell (CAR-T cell) receptor technologies to genetically engineer T cells to recognize and kill cancer. Several product candidates have shown compelling clinical responses in clinical trials in refractory leukemia and lymphoma conducted to date.  This acquisition will position Celgene to become a preeminent cellular immunotherapy company with a platform to be at the forefront of future advances. JCAR017, a pivotal stage asset, with an emerging favorable profile in DLBCL, is expected to add approximately $3 billion in peak sales and significantly strengthen Celgene’s lymphoma portfolio, and JCARH125 will enhance Celgene’s campaign against BCMA (B-cell maturation antigen), a key target in multiple myeloma.  +++++  The global pharma industry is undergoing a dramatic transition from a quest for blockbusters to the design of a precision medicine based drug design. Artificial intelligence is one of the most prominent elements that has been adopted as part of the transition from a fully integrated pharmaceutical company model of drug design to extensive interaction with smaller innovative R&D companies as well as academic institutions.  Artificial Intelligence (AI) is the activity devoted to making machines intelligent, and intelligence is that quality that enables an entity to function appropriately and with foresight in its environment (definition proposed by Nils J. Nillson, Stanford U.). Even though there are numerous definitions for AI, this one fits nicely into the goal of using machine learning for improving the rate of success in the design of novel and cost-effective therapeutics.  One of the primary reasons that AI has such a great potential in drug development is that there is a huge amount of health data available right now in the public health system. Clinical trials’ data, electronic medical records (EMR), genetic profiles and much more is the wealth representing the notion of BIG DATA in healthcare. The main challenge regarding the processing of big data is the need to process it in a meaningful and cost-effective fashion. That is why training a machine to fulfill the task becomes so attractive. Selecting and adjusting the right algorithms is the first essential step but once it is in place, training machines to find optimal patterns between the structure of “druggable molecules” and their optimal activity is within reach.  Canada has established a leadership position in training of machines to learn how to perform complex tasks, in a relatively short period of time. Based on recent commitments to the space, it is expected that we will witness in the foreseeable future designs of novel and much more specific therapeutics with higher potency and lesser side effects. The prospects are quite encouraging in light of the shift global pharma industry is adopting towards precision medicine. That shift will rely on sifting through patients’ medical records. Canadian AI machines are learning fast and are expected to become a key player in advancing academic concepts into standard and streamlined processes and organizations. In Ontario, the University of Toronto has emerged as a world-leading hub for research and entrepreneurship in this area. A potent combination of long-standing academic research in conjunction with the adoption of machine learning methodologies have already proven to be game-changing opportunities. Interactive approaches to computer science and medical research, combined with emerging best in class entrepreneurship programming and training is already yielding some fascinating fruits in the area of AI for drug discovery.  Companies like Structura Bio are taking the complex computational challenge of reducing noisy images from cryo-electron microscopes into readable highly accurate 3D structures of proteins and are doing what used to take a server room filled with computers a week, in a matter of seconds. Similarly, Phenomic AI (a recently incorporated UTEST company) uses a technique called deep learning to analyze data from high-throughput phenomic screens to analyze cell and tissue phenotypes in microscopy data with incredible accuracy. It holds out the potential for eliminating human intervention in the assessment of all that data. In some cases, companies like Deep Genomics and Atomwise are going all the way by leveraging their respective AI technologies to become drug discovery engines themselves. Our awareness of the impact of the AI revolution in drug discovery is already enormous and we’re only at the beginning of its adoption cycle. Future advances in Canada will be buoyed further by strong academic and institutional foundations that have been put in place to assist Canada in sustaining this advantage. The Vector Institute, as an example, was established in 2017 in partnership with Canada’s largest companies and the Federal and Provincial Government’s to attract and retain world-leading research talent and to promote cutting-edge research in the field.  Recently, partnerships have been established between the MaRS Innovation research healthcare ecosystem (UHN, Sickkids, Sunnybrook) with global players in the space of machine learning based drug design and developments. Partnerships with Schrödinger and Evotec have been established to capture the enormous potential of “fishing in the pond” of EMR’s rich source of unraveling the tissue/cellular architecture as a baseline for the discovery of novel disease targets, which thereby establishes a mechanism for better drugs.  The field of AI in the service of medical research is still in its infancy, but the initial avalanche of results is already starting to give us an idea of the great potential that machine learning can offer to those embarking on advancing drug development. Reducing screening times, aiding new drug candidates and finding the most effective drugs for specific diseases at a speed that humans cannot achieve is compelling, and we believe that AI will increasingly become part of the medical landscape. Once hurdles such as data standardized collection and storage as well as data privacy concerned are addressed, it is expected that we will witness an exponential inclination in the implementation of machine learning as a powerful tool in the design of more potent drugs with lesser side-effects. The FDA and Health Canada are encouraging pharmaceutical companies to join the choir.  To conclude, rephrasing from Eric Topol of the Scripps Research Institute (CNBC, May 2017), “The potential of artificial intelligence has probably the biggest impact of any type of technology on healthcare.”  +++++  Two of Canada’s largest producers of cannabis have struck a deal after months of negotiations and a hostile takeover bid. The board of directors and the special committee of the CanniMed board have agreed to support a new offer made by Aurora for the acquisition of all of the issued and outstanding shares of CanniMed not owned by Aurora.   Terry Booth, the CEO of Aurora Cannabis says, “We are very pleased to have come to terms with CanniMed on this powerful strategic combination that will establish a best-in-class cannabis company with operations across Canada and around the world.”   The new offer for CanniMed is approximately $1.1 billion based on Aurora’s implied share price of $12.65. The maximum amount of cash available under the amended offer will be $140 million, and the number of Aurora shares to be issued will be between approximately 72 million and 84 million. Assuming maximum cash elections, each CanniMed shareholder would receive $5.70 in cash and 2.9493 Aurora shares.  Despite CanniMed filing a law suit against Aurora earlier this month, this deal provides the optimum outcome for both companies.  +++++  The Ottawa Hospital has been awarded $12.7 million in the most recent project grant competition from the Canadian Institutes of Health Research (CIHR). The grant funding will be going to sixteen research groups at the hospital who are in affiliation with the University of Ottawa. This represents an enormous success rate of 30 per cent, doubling the national average.  The new funding will provide researchers the much-needed capital to delve deeper into their studies ranging on a plethora of subjects – anywhere from oncolytic viruses as immunotherapy treatments, using a holistic approach to improving the quality of life for the homeless, to understanding the role of liquid metabolism in the brain.  “I’m delighted that our researchers have once again achieved such a high success rate,” says Dr. Duncan Stewart, executive vice president of research at The Ottawa Hospital and professor of medicine at the University of Ottawa. “These new research projects have the potential to redefine the future of health-care, both at home and around the world.”  The Ottawa Hospital has scored above the national average in CIHR grant competitions for the past several years, including 2015, 2016, and 2017. This research centre shows great promise and innovative studies for the years ahead.  For the summaries of all the projects please visit biotechnologyfocus.ca   +++++  Well that wraps up another episode of Biotechnology Focus radio. If you have any questions, comments or story ideas, please contact us at press@promotivemedia.ca, and don’t forget to follow us on our twitter handle @BiotechFocus. From my desk to yours – this is Michelle Currie.    

076 | Regulations, Drug Discovery, and Collaborations Welcome to another episode of Biotechnology Focus radio. This week we’ll be discussing regulations when working with drugs, financing drug discoveries, and an East Coast collaboration that will develop new opportunities for marine biotechnology. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene. +++++ Health Canada maintains tight control over the sale of drugs in Canada by applying the Food & Drug Regulations to all involved parties. In order to bring a drug product to market, a manufacturer must provide evidence to Health Canada on drug safety and efficacy, and demonstrate that processes planned for production are consistent with the regulations. Enforcement of the regulations is not limited to the pre-approval phase. After receiving approval, license holders must continue to ensure that all parts of their supply chain operate in compliance with Health Canada regulations. Logistic partners including importers, distributors and wholesalers are required to operate in compliance with the Good Manufacturing Practices (GMP) section of the regulations when working with drug products so that procedures in place do not adversely affect the quality of drugs. The GMP is broad in scope and covers numerous areas of responsibility such as building design, sanitation practices, distribution records/inventory control, record keeping and testing of products where necessary before they are made available for sale. One important aspect of GMP requirements is the stipulation that all procedures involving drug products are performed according to written procedures and are to be performed by qualified and trained personnel at all times. For some groups in the supply chain, this high level of accountability may not be achieved without significant updates to operational procedures or investments in additional staffing or equipment. The term “GMP” is recognized worldwide as the quality standard for drug products. However, how companies receive certification from their local regulatory bodies vary throughout the world. In some regions, GMP regulations have been enacted by a federal authority, but the actual approval of GMP compliance is not managed by that same authority, and instead, certification is provided by third-party auditors (for example the FDA in the United States). Health Canada has a unique system whereby evidence to demonstrate GMP compliance is approved directly by Health Canada before facilities are permitted to carry on activities with drug products. This pre-review system of GMP evidence may pose a barrier to entry for some groups looking to get into the drug product business, and is a frequent hurdle for importers wishing to bring drug products into Canada for further sale. Up until a few years ago, Health Canada’s efforts in GMP regulation and compliance were focused primarily on drugs in finished form. However, over time it became evident that regulating starting materials, otherwise known as active pharmaceutical ingredients (API) were also a crucial part of the process of ensuring the quality of finished drugs. Health Canada, therefore, made a significant update to the GMP regulations in 2013 by expanding their scope to include API sources. Given that a large proportion of API sources are located abroad, the recent adjustment to the GMP regulations has resulted in an increased regulatory burden for Canadian importers of drug products and manufacturers of drug products; particularly if they are sourcing API from numerous foreign facilities. Challenges for the drug supply chain with respect to GMP compliance may rise as the trend toward outsourcing and increased use of third-party distribution centres continues. It remains the responsibility of the drug product license holder to ensure that all locations involved in bringing their drugs to market in Canada are GMP compliant. Planning for GMP compliance at early-stages of negotiations with contractors can assist with minimizing delays and interruptions in supply chains and production of drug products in Canada. ++++++ CQDM (Quebec Consortium for Drug Discovery) and Brain Canada announce a $1 million nondilutive funding to AbCellera and the University of British Columbia. AbCellera will also be contributing $450,000 to the project, which will expand and apply its state-of-the-art microfluidic antibody discovery platform for the detection of function-modifying antibodies against G-protein-coupled receptor (GPCR) targets. The CQDM support was made possible by the financial contributions of five of its industrial members, including GSK, Janssen Pharmaceutical Companies of Johnson & Johnson, Merck, Pfizer, and Sanofi. These contributions underscore their commitment to driving innovation that can expand the accessible target space of antibody-based therapeutics, the fastest growing class of drugs. AbCellera, started in Carl Hansen’s laboratory at the University of British Columbia in 2012 has become a reputable name in antibody discovery from natural immune repertoires. AbCellera’s microfluidic singlecell screening platform allows for deep profiling of natural immune responses with an unmatched combination of throughput, speed, and assay capabilities. This funding will allow AbCellera’s to further expand its leading capabilities for antibody discovery against high-value complex membrane proteins that have proven intractable by conventional approaches, including hybridoma, phage and yeast display. The continued collaboration between AbCellera and the University of British Columbia is a model example of how public-private partnerships can efficiently translate cutting-edge research into practical applications to accelerate the discovery and development of new therapies for patients. Carl Hansen commented that, “AbCellera is now the recognized leader for antibody discovery against difficult membrane protein targets. To date, they have run successful discovery programs on six GPCR or ion channel targets. Their technology has vastly outperformed what is possible by classic hybridoma and display methods, has succeeded in generating hundreds of unique antibodies per target, and has provided leads to advance partner programs that were otherwise stalled.” This collaboration, will further expand AbCellera’s technology to enable direct cell-based assays capable of selecting ultra-rare antibodies with function-modifying properties. When combined with the throughput and speed of their platform, it will create game-changing capabilities for targeting complex membrane proteins.” ++++++ Thanks to a University of Toronto’s antibody engineering technology, a new cancer immunotherapy has received a US$62 million helping hand in its development. The therapy called, Myeloid Tuning, has been designed to boost the body’s anti-tumour immunity by removing cells that normally hinder or halt the immune system using engineered antibodies. They were developed at the University of Toronto’s Toronto Recombinant Antibody Centre (TRAC). Sidhu originally co-founded TRAC with Professor Jason Moffat as a state-of-the-art antibody engineering platform at the Donnelly Centre for Cellular and Biomolecular Research, where they are both coincidently faculty members. Engineered antibodies are becoming increasingly more popular, as their uses are more precise and will target any molecule or cell type for which they were designed. It is new therapy like these that are leading to a new generation of immunotherapy drugs. The research collaboration between Sidhu, Moffat and Max Krummel, a professor at the University of California San Francisco (UCSF), five years ago has led to myeloid tuning. In 2011, Krummel co-invented the first engineered immunotherapy against skin cancer. Three years later, Sidhu and Krummel cofounded Pionyr Immunotherapeutics in San Francisco to turn research ideas into something more concrete. Pionyr announced recently that it raised US$62 million from investors, bringing their total funding to $72 million. The funds have been raised over the course of two years to develop myeloid tuning into a form that will be compatible with humans. The funding boost came on the back of promising proprietary data obtained with antibodies created in Toronto. So far, Myeloid Tuning has been shown to be effective in multiple mouse tumour models. Starting from scratch in 2010, TRAC has grown immensely and become a sought-after platform with more than 50 ongoing collaborations worldwide. Moffat and Sidhu want to see a continual growth of new drugs developed in Toronto. Thanks to the support of philanthropist Terrence Donnelly, whose ongoing donations have founded the interdisciplinary biomedical research institute, Donnelly Centre, to support research and innovation. The most recent $10 million gift will be used to launch a new hub for biotechnology startups that will accelerate the translation of its research discoveries into new therapies. Its first occupants will be Systems Biologics Inc. and SciGenom Life Sciences, Canada, new Canadian corporations that will develop TRAC antibodies into treatments for cancer and other major diseases. +++++ Croda International acquires Nautilus Biosciences Canada Inc. The two companies already have a proven track record of successful collaborations during the past six years developing specific applications for skin care and hair care, as well as crop care. Croda intends to establish Nautilus as a Croda Centre of Innovation for Marine Biotechnology at the existing base at the University of Prince Edward Island. Through this acquisition and associated patents, Croda will utilise Nautilus’ innovative science for applications across all its market sectors. This location is ideal for biotechnology research and has already attracted and facilitated partnerships with many other biotechnology-based companies. Nautilus has exclusive global access to the Marine Microbial Library which is based at the University of Prince Edward Island. The founder of Nautilus, Russell Kerr explains that they have enjoyed a very positive and collaborative relationship with both Croda and the University of Prince Edward Island for a number of years and have always been impressed with Croda’s drive to develop the opportunities from marine biotechnology. Becoming part of the Croda group will provide Nautilus the resources and support to establish a key centre for the research and development of marine-derived natural products, as well as providing Croda new products for commercial success. Nautilus was founded in 2007 by professor Russell Kerr and, together with its world-class scientists, focuses on using marine microbial biodiversity to discover novel actives and materials. Roy Francis, executive director of the PEI BioAlliance adds, “Croda’s investment in Nautilus and Prince Edward Island is a great return on everyone’s commitment. It’s how a cluster works.” +++++ Well that wraps up another episode of Biotechnology Focus. For the full stories, please visit the website biotechnologyfocus.ca. Thanks again for listening! From my desk to yours – this is Michelle Currie.

075 | Partnerships, potential cures and pandemics      Welcome to another episode of Biotechnology Focus radio. This week has brought new partnerships and novel research to light from across Canada.   An international partnership sets its sight on developing a cure for Alzheimer’s disease  A recent study on Huntington’s could aid cognitive decline  Research suggests link between mortality rates of influenza pandemics   And implanting a potential cure for type 1 diabetes   Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene.    +++++    A deal has been signed between the Krembil Research Institute and French multinational pharmaceutical company, Servier, for the development of a potential disease-modifying drug for Alzheimer’s disease.  This strategic research partnership agreement with Toronto-based company Treventis Corp., a company founded by the director of Krembil, Dr. Donald Weaver, is to co-develop a lasting treatment. Studies are already underway the University Health Network (UHN).  Dr. Donald Weaver stated that “this was a very bid deal. Drug discovery is a tremendously competitive field and this partnership demonstrates the ability of Krembil and UHN to achieve a level of excellence on the world stage. It also helps cement our place as one of the leading neuroscience research facilities in Canada.”  As part of the collaborative agreement, researchers from both countries will be targeting two key proteins that have been identified with memory loss.  Weaver’s team has been working on a therapeutic strategy for near two decades to slow or stop this degenerative disease. Currently, there are no disease-modifying treatments on the market to prevent or stop the progression altogether. Alzheimer’s disease affects over 564,000 people in Canada and is expected to rise to a distressing 937,000 by 2031[1].  In 2013, Treventis was awarded $4.7-million in funding from the prestigious Wellcome Trust to investigate compounds, with the hopes of designing a drug that can safely and effectively treat people with chronic neurological dementias, such as Alzheimer’s. Funding from the Wellcome Trust, a British-based independent charity, is extremely competitive, difficult to obtain, and is traditionally awarded to researchers in the U.K.  Some of the donors and contributors to the advancement of this research are the Brain Campaign, Alzheimer Society of Canada, Canadian Institutes of Health Research, The W. Garfield Weston Foundation, Bright Focus Foundation, and the Krembil Foundation.  As part of the agreement, Servier will fund all research costs and maintain worldwide rights to develop and commercialize drugs advanced during the partnership, while the Toronto researchers set to discover a candidate for a phase I clinical trial.    +++++    A York University study might have found a new treatment option for Huntington’s disease. Christine Till, a psychology professor at the university wanted to know if working memory – a mental workspace that stores information while carrying out a task – training would help early-stage patients with the disease.  In collaboration with the funder, North York General Hospital (NYGH), she led the study where nine patients received working memory training. The results were published in the journal PLoS ONE and detailed how seven of the nine participants completed the training and perceived benefits.  Huntington disease, is a genetic brain disorder characterized by cognitive decline. It is often accompanied by mood changes such as anger, depression, and anxiety. Symptoms usually start when the patient is between 30 and 50 years of age.  The Huntington Study Group estimates that there are between 4-7 individuals per 100,000 diagnosed with Huntington’s in Canada. This number is up for debate largely due to people fearing to take the test because of possible genetic discrimination from health insurers.  This was a pilot, small study aimed at figuring out feasibility, time and costs. It allows researchers to tweak it before running a comprehensive study.  Previous studies of early-to-moderate stage Huntington disease had focused on improving motor functions like gait and balance. Till became encouraged by studies that demonstrated how mice, who were characterized as having genetic mutations mimicking Huntington disease, had benefited from environmental enrichment. These mouse models showed that an enriched environment could enhance motor activity and reduce brain loss.  Inspired by this research, Till began to construct home-based computerized training programs to enhance mental activity in participants with Huntington’s disease.  Participants underwent neuropsychological testing at North York General Hospital or York University twice – once, at the start of the study, and once one week after the completion of the training. This testing was comprised of 90 minutes of questionnaires and neurocognitive assessments.  The training itself involved 25 sessions that were run through the internet and each lasting 40 to 50 minutes. Training was typically completed over a five-week period, five days a week, using the patients’ home computers.  It consisted of exercises that targeted visual-spatial working memory and verbal working memory. Task difficulty was taken into account and adjusted automatically so that the exercises were consistently engaging.  A training coach called the participants weekly to inquire about their experience with the program and to provide motivational support and note any changes in health. Additionally, the training program provided feedback to the participant after each trial was completed. It calculated this by showing comparisons of previous scores and high scores, and providing auditory comments such as “Way to go!” when the participant’s response was correct. Daily performance on the training program was tracked by the computer.  Exit interviews provided powerful insights into the progress of the program and its effectiveness.    +++++    New research out of McMaster University and the Université de Montréal suggests that people who were born during a time of an influenza pandemic are at a higher risk of mortality amidst another pandemic arising. While typically, one develops an immunity from exposure to similar, or sometimes different, influenza A viruses, researchers are expressing that there might need to be exceptions to this rule.  The new data that was collected proposes that people who were born the time of the 1957 H2N2 or Asian Flu pandemic were at a higher risk of dying during the 2009 H1N1 Swine Flu pandemic, as well as the resurgent outbreak in 2013-2014.  The influenza virus has posed a great threat to humanity throughout the years. Its ability to cause widespread pandemics, leaves researchers and scientists scrambling to find a cure. Over the last 100 years, at least five notable pandemics have occurred. This includes the 1918 H1N1 Spanish Flu, the 1957 H2N2 Asian Flu, the 1968 H3N2 “Hong Kong Flu”, the 1977 Russian Flu, and the 2009 H1N1 Swine Flu.  The results align with at least two previous influenza A virus pandemics, in 1918 and 1968, when there were higher death rates among those born during previous pandemic years in 1890 and 1918, respectively.  Matthew Miller, senior author of the paper, and assistant professor of biochemistry and biomedical sciences at McMaster University suggests that this phenomenon is not unique. He believes that exposure to pandemic influenza early in life is a risk factor for mortality during subsequent cross-strain pandemics.  Further research is required to develop appropriate vaccines.     +++++    The University of British Columbia and Vancouver Coastal Health are testing a radical way to cure diabetes. The researchers are implanting pancreatic cells grown in a lab from embryonic stem cells to replace ones previously damaged. The hope is that the implanted cells would mature and multiply to eradicate the reliance on insulin and everyday monitoring of blood sugar via finger pricking.    Dr. David Thompson, a principal investigator in the clinical trial, says that, “If these replacement cells restore a person’s ability to produce their own insulin when needed, it would prevent dangerous episodes of low blood sugar and lessen the complications resulting from high blood sugar, such as blindness, heart attacks and kidney failure.”  The trial could involve about 10 or more people in Vancouver with a severe form of type 1 diabetes, in which a person’s immune system attacks the pancreas, degrading or eliminating its ability to produce insulin.  The team received a grant from the Stem Cell Network of Canada for $500,000 to implement these treatments. Currently, they have only implanted one person, but intend to implant more in the coming weeks. Participants will be followed for two years to see if the implanted cells mature into insulin-producing beta cells and other cells capable of controlling a person’s blood sugar, and whether there are significant side effects.  The implants are part of a larger clinical study by ViaCyte that plans to test the cell-replacement therapy on approximately 40 patients between the US and Canada. ViaCyte has developed a technique for coaxing the embryonic cells along a path to become mature pancreatic cells. The company has also developed for the clinical trial, a protective packet – smaller than a VISA card – that will be implanted just beneath the skin. The packet’s membrane will allow blood vessels to permeate inside so that oxygen and other nutrients will stimulate them to differentiate further. The researchers expect some of the cells will become beta cells, which sense blood sugar levels and release insulin when needed.  As well as these packets, other smaller “sentinel” packets will be implanted and taken out at an earlier stage to evaluate the condition and the development of the cells inside.  With the intention to prevent the participants’’ bodies from rejecting the units, they will be taking immunosuppressants. This, however, makes the patients more susceptible to other infections and is therefore only being clinically tested on people who have a particularly dangerous form of type 1 diabetes.  The procedure for implanting the cells, performed by a team led by Dr. Garth Warnock, a UBC surgery professor, is similar to transplanting clusters of beta cells, known as “islets,” from deceased donors – a treatment pioneered at the University of Alberta. If this clinical study is successful, it could be a promising lead to a cure for type 1 diabetes.    ++++++    Well that wraps up another episode of Biotechnology Focus. For the full stories, please visit the website biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.      

074 | An unprecedented act of kindness, a jump in cancer immunotherapy, and trusting your gut On this episode of Biotechnology Focus radio are some of the top stories this week: How an unprecedented act of kindness will transform lives Promising news out of Ottawa that could take cancer immunotherapy to the next level How a known anti-psychotic has the possibility of being a solution to ALS And how a researcher’s gut reaction turned out to be right. ++++++ Making headlines this week is about the staggering $100 million anonymous donation that was received by the Centre for Addiction and Mental Health (CAMH) in Toronto to combat the causes of mental illness and develop cures to save lives and further hope. This anonymous gift leaves many incredulous and excited to fuel discovery and create social change for all Canadians. The donor made a comment on how they had seen first-hand the impact mental illness has on individuals and their families, and that they just wanted to support the next generation of researchers so that they can transform care. This investment has presented CAMH the opportunity to create the Discovery Fund, aimed to transform the lives of those touched by mental illness. The fund will attract talent, explore innovative ideas, support young scientists and leverage data to pick the brain and uncover how the pieces fit together. Dr. Catherine Zahn, the president and CEO of the Centre for Addiction and Mental Health said that “Complex problems need complex solutions. We need to invest in the fundamental research and the clinical innovation that will improve the health of individuals and populations, locally, nationally and globally. This gift will make that a reality.” +++++ The Ottawa Hospital and the University of Ottawa have released a promising study. It suggests that combinations of two immunotherapies – oncolytic viruses and checkpoint inhibitors – could be more successful as treatments for combating triple-negative breast cancer than traditional methods. The study was published in Science Translational Medicine using mice models by Dr. Marie-Claude Bourgeois-Daigneault, lead-author of the study and postdoctoral fellow, and Dr. John Bell, a grantee from the Alliance of Cancer Gene Therapy (ACGT), professor at the University of Ottawa and senior scientist at the Ottawa Hospital. Cancer immunotherapy has become a prominent tool in the treatment of cancer, especially melanoma and leukemia, but has not had such a strong effect on solid tumour cancers. The researchers studied three mouse models of triple negative breast cancer and found that all were resistant to a checkpoint inhibitor which is commonly used to treat other kinds of cancer. They also found that while an oncolytic virus called Maraba could replicate inside these cancers and help the mouse’s immune system recognize and attack the cancer, the virus alone had minimal impact on overall survival. The researchers decided to up the ante and put both the oncolytic and checkpoint inhibitor in unison to determine if the results would change in models that mimicked metastatic breast cancer. They found that this combination cured 60 to 90 per cent of the mice, compared to zero for the checkpoint inhibitor alone and 20 to 30 per cent for the virus alone. In these models, the virus was given previous to the surgery and the checkpoint inhibitor was given afterward. There are other ongoing clinical trials that are testing oncolytic viruses, such as Maraba, in aggregation with checkpoint inhibitors in people with cancer, as well as expanding the use of oncolytic viruses to fight other infectious diseases, such as HIV. These results could be a breakthrough and make this an incredibly exciting find. +++++ Most people are familiar with the Ice Bucket Challenge that went viral a couple years ago to raise awareness for amyotrophic lateral sclerosis, or more familiarly known as ALS. It topped the charts with over $17 million participants that raised a substantial amount of money for the cause. So where did these raised funds go? Well, some of that capital has been invested into a research study at the University of Calgary to investigate a potential pre-established drug for use as a treatment for ALS. Dr. Lawrence Korngut, associate professor at the Cumming School of Medicine and a member of the Hotchkiss Brain Institute, is spearheading a clinical trial associated with nine hospital centres around Canada to determine if a well-known anti-psychotic drug could be repurposed to either cure or treat symptoms of ALS. Studies from researchers in Montreal indicated that the use of pimozide to stabilize mobility was receptive in animal models who were born with the equivalent of human ALS. They discovered that the drug had a particular knack for preventing paralysis in fish with a genetic form of ALS by preserving the neuromuscular function – which can be related to the disease in humans. After only six weeks, the research team started to see results of the drug’s effectiveness. One of the first more typical signs of ALS – which is the loss of control of the thenar muscles – maintained normal functioning. However, it is not known yet if pimozide can be repurposed for this disease. More studies will be necessary to determine if this will only have a stabilizing effect, or if it is curative. It appears as if things are looking up for ALS patients as more clinical trials are introduced, but there is still no definitive cure for the disease. More ALS patients are needed for these studies. Any who are interested in participating please contact pimozide2@ucalgary.ca. +++++ Many people around the world rely on catheters every day to empty their bladder – especially people with spinal cord injuries. After a well-respected publication concluded that catheters could be reused without an increased risk of infection, a professor and researcher from the University of British Columbia began to question. Dr. Andrei Krassioukov, a professor of medicine at UBC and chair of rehabilitation research with International Collaboration On Repair Discoveries (ICORD), who works closely with groups such as the American Paraplegic Society, and the Canadian Association of Physical Medicine and Rehabilitation, just this past summer spoke to a few of the wheelchair athletes that participated in the Summer Paralympics in London about the single-use versus multiple-use issues on catheters. A urinary tract infection (UTI) is an infection in any part of your urinary system — your kidneys, ureters, bladder, and urethra. Most infections involve the lower urinary tract — the bladder and the urethra. It can be an extremely painful and incapacitating infection. Antibiotics like amoxicillin, are used to heal the infection and soothe the symptoms. Sexually active women and patients that use catheters, like spinal cord injury patients are at higher risk. It has been a debate amongst the medical community of whether or not to reuse catheters. The instrument can cost anywhere from $5 to $30, and for people with spinal cord injuries that require a new one every time they release their bladder, it begins to add up. Around the world, and even within Canada, there are price and coverage differences for the individual. In France, it is illegal to reuse catheters; and in other countries, they simply can not afford the healthcare costs of single-use. Cochrane Canada, a non-profit, non-governmental organization formed to organize medical research findings to facilitate evidence-based choices about health inventions, reviewed evidence from 31 clinical trials of single vs. multi-use catheters and urinary tract infections in 2014. Their statement is that there was no convincing evidence that the incidence of infection was linked by catheterization. From Krassioukov’s clinical experience and study conducted at the Paralympics he instinctively knew that these results were false. He assembled a team of experts from around the world to re-examine the evidence. Due to the sufficiency of the errors they found in the previous concluding evidence, Cochrane has since withdrawn their conclusion. While there have been new developments on how to make catheters sterile and ready for multi-use, they have yet to be fully confident that it will not reimpose infection. +++++ Well that wraps up another episode of Biotechnology Focus Radio. If you are interested in contributing an article to Biotechnology Focus, please email us at press@promotivemedia.ca. For the full stories of this week’s headlines, check out biotechnologyfocus.ca. Thank you all so much for listening. I hope you are having a great week and tune in soon again! From my desk to yours – this is Michelle Currie.

Happy 2018 from Biotechnology Focus! Ahead on today’s episode are some of the headlines that are shaking things up in the new year.   Sanofi launches digital clinical trials for increased probability of participation  A repurposed drug could be the key to successful stem cell transplants  Experts advise caution of the use of Sanofi’s dengue vaccine as new warnings are added to the label  Virus vs. Virus – could Maraba knock out HIV?  Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene.  +++++  First up this week, Sanofi launches a digital way to partake in clinical trials – to make participation more widely available and lower the duration of the trial itself. Clinical trials are a crucial step to putting the potentially life-saving medication on to shelves. However, due to the specifics required for each participant and their proximity to a research centre, 80 per cent of clinical trials are delayed due to recruitment problems in the US alone according to a study by the Centre of Information and Study on Clinical Research Participation (CISCRP).  Unfortunately, these delays prevent some of these innovative medicines from reaching its patient base or taking longer than necessary. Sanofi, partnering with Science 37 decided to tackle this problem head-on by taking a digital approach.  According to the study by Centre of Information and Study on Clinical Research Participation, 87 per cent of patients are willing participants for clinical studies, but yet 70 per cent of them live over two hours away from a research centre – deterring them. Many studies require the participant to check in a few times a week, which is too far for most people to attend during their busy lives.  Science 37’s approach allows patients to be monitored and report to researchers via an Apple iPhone equipped with the company’s NORA technology. Qualified study participants are provided with the phone, a data plan, any sensors or any devices needed to obtain the information for the study. With quick access to researchers, mobile nurses and under the care of local health care professionals, this could be a solution the geographical gap.  Sanofi’s agreement with Science 37 covers use of its Metasite model and NORA technology across the U.S. with plans to expand internationally in the future. By eliminating months of searching for patients and long travel time to study sites, virtual clinical trials could reduce total trial time by as much as two years.  +++++  Canada is known for its long track record of success in stem cells, specifically in blood stem cells, and the research from British Columbia will be no exception. Peter Zandstra, a founder and chief scientific officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and director of UBC’s new School of Biomedical Engineering, as well as researchers from UofT and UBC, publish in Science Translation Medicine, a potential way to repurpose an anti-inflammatory drug for blood stem cell transplants.  Earlier work looked at cell interaction and signaling between cell population where the researchers noticed that one of the growth factors tumour-necrosis-factor-alpha (TNF-a) – a protein that cells deploy against infection, which is sometimes overproduced, killing healthy cells – had a negative effect on blood stem cells. This observation emerged when the researchers did not get the expected number of stem cells to rise to mature blood cells during blood stem cell transplantation. This finding influenced Zandstra to explore whether one of several existing drugs that block TNF-a would allow human blood cells to thrive in a new host.  Zandstra and his team added the blocking agent either with the transplant or up to two weeks later. The results they received from testing on animal models far surpassed expectations. The mice had numerous more blood stem cells, and more importantly, diversification – more rapid T and white blood cells, which suggested a healthy transplant.  Zandstra had stated that this could lead to using smaller grafts, and would provide two main benefits. The first being that there are many of those available with a large pool from which to choose; and second, the potential to have better matches from those existing pools. A significant portion of banked umbilical cord blood is simply not suitable for use on adults because they are either too small or not appropriately matched.  These results provide a strong basis to advance the research to clinical trial and observe whether TNF-a blockers improve patient outcomes or save lives. This repurposed drug could be the key to successful stem cell transplants.    +++++  If you’re thinking about going on holiday this winter season and deciding which vaccines to get for your trip – experts at World Health Organization are advising caution of the use of Sanofi’s dengue vaccine, at least for now. The vaccine, could be putting people, especially children, at a heightened risk of severe disease.    Sanofi recently changed the warnings on the label of their vaccine, Dengvaxia, even though experts from the World Health Organization (WHO) had told them a year previously that the vaccine had safety risks and should only be used in people who have had a previous dengue infection.  Based on six-years of clinical data, the analysis from Sanofi that evaluated the long-term safety and efficacy of Dengvaxia in people who had been infected with dengue previously and with those who had not, confirmed that it should only be used in people who had a previous infection and over the age of 9 in dengue-infested regions. The age recommendation coming from surveillance data which indicated that 70-90 per cent of people will have been exposed to dengue by the time they reach adolescence.  Dengue, a mosquito-borne viral disease is painful and debilitating, for which there is no treatment. Approximately 4 billion people are at risk of dengue fever. It hits hardest in rainy seasons around tropical areas and can be lethal. There are five strains of the virus, but only one will provide the infected with anti-bodies for lifelong immunity. The other strains will, unfortunately, have a short-term immunity, leaving the infected with the potential of subsequent infections that can cause severe complications.  The vaccine, which can act as a first infection to those who have not been infected with dengue before, has been approved in 19 countries and launched in 11. The Philippines, who had invested a hefty sum into the dengue vaccination program recently pulled the vaccine off the shelves after Sanofi’s statement that the vaccine could cause “severe disease” was released. The country braces for the worst after hearing this news and after the immunization of over 730,000 children.  Sanofi urges physicians and health authorities to update the information regarding the vaccine.  +++++  Researchers at the University of Ottawa and the Ottawa Hospital discover that the Maraba virus, or MG1, is effectively targeting and destroying the kind of HIV-infected cells that standard antiretroviral therapies can not reach. These findings were published in the Journal of Infectious Diseases and may very well help lead to a cure for HIV in humans.  While there are certain “cocktails” that are taken daily by people who have been diagnosed with HIV, there is no current cure for the disease, even when the cells lie dormant and a person is deemed “undetectable”. “Undetectable” meaning that they are undergoing antiretroviral therapy and their white blood cell counts have increased and their viral load significantly decreased to an “undetectable” level – but there it lies in wait – for the virus load will quickly rebound if one of these “cocktails” are missed.  These latent HIV-infected cells are hard to target because they are not distinguishable from normal cells. Dr. Jonathan Angel’s team had decided to try an innovative approach to identifying these dormant cells using the MG1 virus. This virus attacks cancer cells that have defects in their interferon pathway, which makes the cells more vulnerable to viruses. Previously, Angel and his team had discovered that latent HIV-infected cells shared this defect.  The research group used several laboratory models of latent HIV-infected cells to discover that the MG1 virus targeted and eliminated the HIV-infected cells and left the healthy cells unharmed.  While most of these cells in patients are in the lymph nodes and other organs, a tiny number are found in the blood. When the researchers added MG1 to relevant blood cells taken from HIV-positive individuals, the levels of HIV DNA in the sample dropped. This indicated that the HIV-infected cells had been eliminated.  Pending funding and approvals, the research team’s next step is to try the virus in animal models of HIV or move directly to clinical trials. Further examination and time will tell whether this is a knockout solution for combating HIV.  +++++  Canada is known for its long track record of success in stem cells, specifically in blood stem cells, and the research from British Columbia will be no exception. Peter Zandstra, a founder and chief scientific officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and director of UBC’s new School of Biomedical Engineering, as well as researchers from UofT and UBC, publish in Science Translation Medicine, a potential way to repurpose an anti-inflammatory drug for blood stem cell transplants.  Earlier work looked at cell interaction and signaling between cell population where the researchers noticed that one of the growth factors tumour-necrosis-factor-alpha (TNF-a) – a protein that cells deploy against infection, which is sometimes overproduced, killing healthy cells – had a negative effect on blood stem cells. This observation emerged when the researchers did not get the expected number of stem cells to rise to mature blood cells during blood stem cell transplantation. This finding influenced Zandstra to explore whether one of several existing drugs that block TNF-a would allow human blood cells to thrive in a new host.  Zandstra and his team added the blocking agent either with the transplant or up to two weeks later. The results they received from testing on animal models far surpassed expectations. The mice had numerous more blood stem cells, and more importantly, diversification – more rapid T and white blood cells, which suggested a healthy transplant.  Zandstra had stated that this could lead to using smaller grafts, and would provide two main benefits. The first being that there are many of those available with a large pool from which to choose; and second, the potential to have better matches from those existing pools. A significant portion of banked umbilical cord blood is simply not suitable for use on adults because they are either too small or not appropriately matched.  These results provide a strong basis to advance the research to clinical trial and observe whether TNF-a blockers improve patient outcomes or save lives. This repurposed drug could be the key to successful stem cell transplants.  +++++  Well that wraps up another episode of Biotechnology Focus. For the full stories, please visit the website biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.    

Ahead of Biotechnology Focus radio are some of the highlights of the week. ImmunoBiochem is haloed with angel investors after completing a new round of financing. Biotalent Canada provides subsidy to fund more “green jobs” for young graduates. eSight named one of the best inventions in 2017 by giving the gift of sight. Zymeworks presents results of ongoing completed dose escalation phase 1 oncology study. Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene. +++++ Our first story this week takes us to the heart of Toronto with ImmunoBiochem Corporation as it completes a new round of financing led by angel investors and the company’s founding investor. The corporation has expanded its operations and is now located at Johnson & Johnson, JLABS, in the centre of Toronto. The company is focused on solving tumour heterogeneity by targeting a class of proteins in the tumour microenvironment with antibody drug conjugates (ADCs). This is an anticancer therapeutics class that combines the selectivity of targeted biologics with the potency of highly cytotoxic small-molecule drugs. One of the highest priorities of ImmunoBiochem is to transform the lives of patients who have triple-negative breast cancer – an extremely aggressive disease that has poor survival rates and does not respond well to major therapies. ImmunoBiochem in partnership with the Centre for the Commercialization of Antibodies and Biologics (CCAB) and the University of Toronto, has developed fully-human antibodies for the treatment of breast cancer and solid tumours. JLABS Toronto is a 40,000 square foot facility located in the MaRS Discovery District. The labs provide a flexible environment for start-up companies pursuing innovative technologies and research platforms for life sciences. Johnson & Johnson does not take an equity stake in the companies occupying their space or in developed products. ImmunoBiochem is a member of the Ontario Bioscience Innovation Organization and is partaking in the OBIO Capital Access Advisory Program. The company is also supported by MaRS Health and the Health Innovation Hub (H2i) accelerator at the University of Toronto. The company will be at the JPMorgan Healthcare week in California next month and is open to additional partnerships and investment. +++++   BioTalent Canada announces the extension of its wage-subsidy program aimed at helping new graduates across Canada gain access to “green jobs”. The federally funded program will provide $2.3 million in wage subsidies and create over 200 new placements over the next two years in biotech, environmental and likewise sectors. Career Focus Green Jobs is a wage subsidy initiate intended to alleviate youth unemployment. It has been funded in part by the Government of Canada’s Youth Employment Strategy. Wage subsidies have a positive record of jumpstarting careers, especially for biotech grads and aiding small to mid-sized enterprises acquire the funds to hire more talent. According to the BioTalent Canada’s 2017 labour market report on youth employment, almost 85 per cent of new graduates retain full-time employment after their wage subsidy ends. BioTalent Canada, a national non-profit HR association for Canada’s bio-economy, has a long track record of successful implementation of wage-subsidy programs and will disburse over $10.3 million in wage subsidies, to create 1,400 job placements over the next four years. The Green Jobs program will form an important component of those new placements. Eligible companies will be those with a sustainable development mission, or those with products or services that directly reduce carbon footprint, enhance recycling or reduce waste. Similarly, positions that are dedicated to those ends from other industries may also be eligible for the subsidy. Companies interested in applying are encouraged to visit biotalent.ca/wage-subsidies for more information. +++++   Time magazine has named eSight one of the best inventions in 2017. After years of challenging work, and millions of dollars, the company was able to develop electronic glasses that actually allowed the blind to see. Inspired by his two blind sisters, the founder had decided to use his engineering skills to find a solution they could live with. The organization believes that everyone deserves to see. This technology has the capability of changing millions of individual lives across the world. It will allow for mobility and freedom and for each person to experience those momentous moments when they can see their loved ones faces, their peers, and a whole new way to virtually see life. Dr. Brian Mech, president and CEO of eSight says that “For eSight to receive this recognition from Time is a wonderful affirmation of the breakthrough work we do on a daily basis to Make Blindness History. eSight’s world-class lab is the largest and most advanced, anywhere in the world, that specializes exclusively in developing clinically-validated medical devices that allow the legally blind to actually see and be independently mobile.” eSight will work on individuals with low vision, and who are legally blind. People who are legally blind have an acuity of 20/200 or poorer in their better eye. Low vision is another term often used, referring to people who have an acuity of 20/70 or poorer in their better eye. The eyes are very complex organs and there are many eye conditions that can cause blindness or low vision. There are many testimonials from legally blind individuals who have used this device can not express enough how much this technology has changed and enhanced their life. The company has seen tremendous amounts of interest from companies wishing to help their blind employees to schools wanting to give the gift of sight to students. Time magazine has aptly named eSight for being one of the best inventions in 2017. +++++   Lastly this week, Zymeworks Inc. presents the completed dose escalation portion of its phase I study of ZW25, a bispecific antibody targeting two distinct domains of the HER2 receptor. The HER2-mediated signaling pathway is perceived to contribute to tumour growth in several cancers. There have been 22 patients enrolled in the study – 11 with breast cancer, eight with gastric, gastroesophageal junction, or esophageal (GE), and three with other HER2-expressing cancers. Part one of the multi-part study was a standard dose escalation where patients received ZW25 either weekly or bi-weekly in cycles of four weeks each. The Study Highlights are: – Six Partial Responses (PR) were observed across all dosing groups. – Clinical benefit was observed in heavily pretreated HER2-high breast and GE cancer patients. – Breast cancer patients received a median of six prior HER2-targeted regimens for metastatic disease; partial response in 56 per cent (5/9) of breast cancer patients with measurable disease, with 89 per cent (8/9) experiencing a decrease in target lesions. – Three HER2-high GE cancer patients with measurable disease displayed shrinking tumours. – ZW25 was well-tolerated at all doses and schedules, with the most common adverse events being diarrhea, infusion reactions, or nausea. – The dose escalation portion of the phase I trial is complete and enrollment in the expansion cohorts is underway. There was a reduction in target lesions per RECIST criteria in 79 per cent of breast and GE cancer patients with measurable disease (11/14). The best overall response (BOR) in 17 patients that had at least one tumour restaging was six in breast and GE cancer patients’ PR (35 per cent), three with SD (18 per cent) and eight with progressive disease (47 per cent). Of the eleven breast cancer patients, all were HER2-high and had received a median of six prior HER2-targeted regimens for metastatic disease. Of the eight GE patients, six were evaluable for response, and had received a median of four prior systemic regimens. Three of five patients with measurable disease had a decrease in tumour size. +++++ Well that wraps up another episode of Biotechnology Radio. We hope you enjoyed it. If you have any feedback or story ideas, please reach out to us via press@promotivemedia.ca. From all of us here at Biotechnology Focus, have a wonderful week ahead. From my desk to yours – this is Michelle Currie.

Ahead on Biotechnology Focus radio are some of the stories from universities across the country and their innovative research this week. The University of British Columbia presents research that Alzheimer’s might be a whole-body problem. The University of Guelph identifies key protein in cancer metastasis. A University of Toronto scientist will be conducting a real-time study of astronauts while on mission. And, Western University’s National Centre for Audiology will be testing a device that may lay the foundation for hearing in the future. Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene.  Our first story this week takes us to British Columbia, where recent studies are showing that Alzheimer’s might be linked to more than just deteriorating brain matter and plaque. It could be a whole-body phenomenon. The findings that were published in Molecular Psychiatry offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain. Instead, the drugs might be able to target areas such as the liver and kidney to flush out the toxic proteins that cause dementia before ever reaching the brain. Weihong Song, a psychiatry professor from the university of British Columbia and Yan-Jiang Wang, a neurology professor at the Third Military Medical University in Chongqing, China, demonstrated the mobility of a protein linked to Alzheimer’s disease through a technique called parabiosis. The technique involves surgically attaching two specimens together so they share the same blood supply for several months. The scientists attached normal mice, which don’t naturally develop Alzheimer’s disease, with mice modified to carry a mutant human gene that produces elevated levels of the protein called amyloid beta. In people with Alzheimer’s disease, that protein ultimately forms clumps, or “plaque”. The findings described the mice who had been attached to an amyloid beta inflicted counterpart ended up “contracting” the disease, all in just a few months. Not only did the normal mice develop plaque, but also a “tangle”-like pathology, which are twisted protein strands that form inside brain cells that disrupt their function to eventually kill them from the inside-out. Other signs of Alzheimer’s-like damage included brain cell degeneration, inflammation, and microbleeds. Even the ability to transmit electrical signals involved in learning and memory were impaired after a brief time being joined. Amyloid beta is produced in other areas of the body besides the brain. It can be found in blood platelets, blood vessels, and muscles. Until these experiments, it was unclear if amyloid beta from outside the brain could contribute to Alzheimer’s disease. It appears from this study, that indeed it can. Perhaps in the near future, researchers and scientists will develop a drug that would tag the amyloid beta biochemically in such a way that the liver or kidney will be able to flush it out before generating damage. +++++++ The University of Guelph researchers have made a discovery during one of their ground-breaking studies. They have identified a protein known as cadherin-22 that binds cancer cells together and allows them to invade tissues. Hindering this protein showed signs of reduction in metastatic cancer patients for breast and brain cancer cells by up to 90 per cent. This study was published in the journal Oncogene and looks specifically at hypoxia in tumours. More solid cancer tumours that are depleted of oxygen, are difficult to treat and replicate at a faster rate. The researchers from the university discovered from the analysis of more than 100 patients with breast or brain cancer that there was a link between the quantity of cadherin-22 and the level of hypoxia in a tumour itself. The more hypoxic the tumour was, the higher the protein count of cadherin-22. Until now, little was known about how oxygen-deprived cancer cells bound together and interacted to spread. The U of G researchers found that it is precisely under conditions of low oxygen that cancer cells trigger the production of cadherin-22, putting in motion a kind of protein boost that helps bind cells together, enhancing cellular movement, invasion, and likely metastasis. The protein is found on the outside of cells and allows hypoxic cancer cells to migrate together. Scientists have known for decades that hypoxia plays a role in tumour growth and metastasis, as well as a poor patient outcome. Professor Jim Uniacke and his team identified that cadherin-22 plays an integral part in the advancement of cancer cells. The researchers used an incubator to monitor cancer cells in a low-oxygen environment comparable to a tumour, where the protein cadherin-22 had been removed via molecular tools. The cancer cells failed to spread. These findings offer vital insights into the aggression and migration of cancer cells. +++++++ A University of Toronto scientist will be performing real-time blood cell analyses on astronauts to reveal how time, space, and speed affect the immune system. Dr. Chen Wang hopes that this research will lead to an understanding of how stress and other environmental factors impact our ability to fight disease. Wang, a professor in the faculty of medicine’s department of laboratory medicine and pathobiology and a clinician-scientist at Mount Sinai Hospital, will be leading the project named Immuno Profile, to study the astronauts on the International Space Station over the course of five years. Canadian astronaut and physician, David Saint-Jacques, will be part of the next mission to the space station and will participate in several Canadian-made health experiments announced by the Canadian Space Agency. The astronauts will use a device that will take finger-prick blood samples during the flight mission, then the information will be sent back to Wang and his team for analysis. Wang expects to see immune cell and cytokine mediator changes, identify different types of immune cells and to see if the cells are functioning well or not. Wang also commented on the uniqueness of the space flight environment to study immune system stressors. Immune dysfunction relates to many diseases, including cancers, viral infections, MS, type I diabetes, and even the aging process. The weightlessness of space can also be used to learn more about the less-understood lymphatic system, which depends on the pressure to flow properly. They hope to develop a new model for how the immune system responds to circadian rhythm and various stresses. +++++++ Lastly for this week, Western University’s National Centre for Audiology (NCA) is testing a new device that may lay the foundation for the hearing of the future. Recently approved by Health Canada and already available in the states, Earlens hearing aid offers a remarkable chance for the hearing impaired to listen in to the everyday world. Its sound-to-light technology eliminates the whistling noise common in conventional hearing aids and delivers the broadest frequency on the market that results in a more life-like sound with crisp highs and rumbling lows. Western University is the first Canadian location authorized to test out the Earlens hearing aid and see if it measures up. Traditional hearing aids are worn behind the ear or in the ear and pick-up, amplify and process incoming sounds and direct them into the ear canal. Meanwhile, the Earlens rests directly on the eardrum and gently activates the natural hearing system. Western’s National Centre for Audiology is a state-of-the-art research centre. It has developed national protocols for pediatric heating assessments, developed methods for fitting hearing aids, has tested numerous devices for more than a dozen companies across the globe and is dedicated to tackling complex issues related to hearing loss. The NCA will be testing the Earlens device using a double-blind study to examine if its light pulse invention turns on the bulb to resonate a way to the future of hearing. ++++++++ Well that wraps up another episode of Biotechnology Radio. We hope you enjoyed it. If you have any feedback or story ideas, please reach out to us via press@promotivemedia.ca. From all of us here at Biotechnology Focus, have a wonderful week ahead. From my desk to yours – this is Michelle Currie.

Hi! This is Michelle Currie and on this episode of Biotechnology Focus radio, we will be discussing outsourcing. A topic defined as “the strategic use of outside resources to perform activities traditionally handled by internal staff and resources.” It is a strategy used by organizations to contract out major functions to specialized providers.  +++++  I have with me today, Michael Stopay, the director from Pacer Air Freight, a Canadian life science logistics company to discuss with us the advantages of outsourcing for small to mid sized enterprises and how his company plays a role.   +++++  Well, that concludes our Biotechnology Focus radio for this week. I would like to thank Michael Stopay for being with us today and hope that you will listen in next week! From my desk to yours – this is Michelle Currie.   

The field of biotechnology is constantly evolving. It encompasses everything that harnesses cellular and biomolecular processes to develop technologies and products that will improve our lives and the health of our planet. This is Michelle Currie with the breaking biotechnology news of the week from Biotechnology Focus radio. Today, I will be discussing how a Canadian drug firm was fined this week for overcharging the U.K. health system roughly £34 million pounds; how the University of Alberta’s researchers have built on the studies from the Edmonton Protocol’s in hopes of making a powerful revolution in diabetes treatment; the release of the first digital pill that will track when it has been ingested; and, how partnerships, like Hoffmann-La Roche Limited and the University of Toronto Mississauga’s Master of Biotech program are fruitful and beneficial – allowing this metropolitan stem hub to reap the awards of such collaborations. +++++++++++++++++++++ Britain’s National Health Services has slapped a £34 million (equivalent to $57.5 million dollars Canadian) to drug company Concordia International for allegedly overcharging the health provider by more than $169 million over a period of 10 years for the sale of a thyroid drug used by thousands of patients. According to the United Kingdom’s Competition Markets Authority, this Ontario-based specialist in generic and legacy pharmaceutical products jacked up the price of its liothyronine drug from £4.46 ($7.54) in 2007 to £258.19 ($436.59) in July this year – that’s an increase of almost 6,000 per cent. The price hike caused Britain’s National Health Services’ bill for the drug to shoot to £34 million ($54.5 million) in 2016 from what was formerly about £600,000 ($1 million) in 2015. The Competition Markets Authority began its price investigations in October 2016 and issued a statement of objection to Concordia and the former owners of the company’s international segment in relation to the pricing of liothyronine in the U.K. from November 2007 to July 2017. The drug company is refuting the allegations of overcharging. However, there have been several instances in the past when Concordia had raised its drug prices. For instance, in May last year, the company raised the price in the U.K. of its eye drops for bacterial conjunctivitis by 5,700 per cent. Concordia was the sole distributor of the medication in the country. The Concordia case is just one of a number of competition markets authority’s cases in the pharmaceutical sector, including a recent fine against Pfizer and Flynn Pharma of nearly £90 million in relation to excessive and unfair prices for anti-epilepsy treatment, phenytoin sodium capsules. Concordia said it will review the Competition markets authority’s preliminary position and that it will continue to “work cooperatively as the CMA proceeds with its investigation.” +++++++++++++++ In the late 1990s, transplant surgeon Dr. James Shapiro and fellow researchers at the University of Alberta developed a method of implantation of pancreatic islets for the treatment of Type 1 diabetes. The work was done by Shapiro and Drs. Jonathan Lakey, Edmond Ryan, Gregory Korbutt, Ellen Toth, Garth Warnock, Norman Kneteman, and Ray Rajotte who would later be known as the Edmonton Protocol. The treatment garnered worldwide attention in the field of diabetes research because seven patients treated with the Edmonton Protocol remained insulin-independent after an average of 12 months. Nearly twenty years later, UAlberta researchers are seeking to build upon the success of the protocol with two novel diabetes trials underway. Dr. James Shapiro commented in a recent interview with the University of Alberta’s journalism site, Folio, that, “today, we’re moving to the next level, expanding on past discoveries and tackling their limitations in the journey toward a powerful revolution in diabetes treatment,” One project involves implanting a device that is as thin as a credit card into a patient. The device will contain human insulin-producing stem cells that are shielded from the body’s immune system. The other research project aims to reverse Type 1 diabetes in newly diagnosed patients. In Type 1, the body’s immune system attacks its beta cells which are responsible for producing insulin in the pancreas, said Peter Senior, an endocrinologist, and member of Shapiro’s research group. He said they are trying a cocktail of drugs that are meant to reprogram the body’s immune system and save the beta cells. However, they have encountered some challenges along the way. In the first project, scar tissue began developing around the implanted device, which blocked the secretion of insulin. This has promoted the researchers to redesign the model of the device to facilitate survival of more stem cells. For further information, please visit the university’s website. ++++++++++++++++++++++++++ The US Food and Drug Administration approves the first-ever digital pill. The pill has its own ingestible digital tracking system embedded into Abilify MyCite to record that the medication was taken. The original product was approved for schizophrenia, acute treatment of manic and mixed episodes associated with bipolar disorder and for use as an add-on treatment for depression in adults back in 2002, but stems to the possibility that this concept could be more widely used in the future. The system works by sending a message from the pill’s sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smartphone or IPad. Patients can also permit their caregivers and physician to access the information through a web-based portal. The mental diseases this pill could stand to benefit are debilitating ones. Diseases that could cause considerable influxes in erratic behaviour that the tracking of medication might help avoid. Abilify MyCite contains a boxed warning alerting healthcare professionals of the possible side-effects that should be heeded, especially with elderly dementia-related psychosis. +++++++++++++++++++++++++ Lastly this week, whether you know Mississauga as “Pill Hill” or “Pharma Alley”, you’ll know that there is some major work going on that has created one of the largest life sciences clusters in North America. Affectionately nicknamed by its residents, Mississauga is tirelessly growing and continuing to build this recently acclaimed second-largest Canadian life sciences hub. The city has an abundance of researchers, scientists, technicians, students and skilled labourers that encompass this booming market. However, it didn’t just happen overnight. During an interview with Ronnie Miller, the president and CEO of Hoffmann-La Roche Limited, Roche Canada, he described Mississauga as having “a lot of first-class research centres”, referring to the many universities and health networks in the surrounding area that make these, plus the number of companies and graduates, quick access to entertainment, the airport, and a highly skilled labour force the perfect place to be. At least one of these institutions has forged a successful partnership with several of the companies that reside in the Mississauga region. The University of Toronto launched their Masters of Biotechnology program at its Mississauga campus back in 2001 with 100 per cent co-op placement since inception and has been working closely with Roche Canada since their first cohort of students in 2002. Many of the past students expressed how the experience they had at Roche was invaluable and that they felt like an employee, as opposed to a co-op student. Likewise, the staff at Roche Canada appreciate the student’s contributions and bring fresh eyes to the table. Mississauga continues to be a growing metropolitan in the greater Toronto area with an ever-expanding sector in life sciences. It has the capacity to attract, train, and retain skilled workers for the biotech sector. Recapturing Ronnie Miller’s statement, “It is the perfect place to be.” ++++++++++++++++++++++ Well that’s it for this week’s update from Biotechnology Focus. For more information on any of the articles please visit our website at biotechnologyfocus.ca. Next week we will be conducting an interview with Michael Stopay, from Pacer Air Freight, about how their family-run life science focused Canadian logistics company outsource and how that can benefit a substantial number of businesses across North America and abroad. From my desk to yours – this is Michelle Currie.

In the previous episode of the Biotechnology Focus podcast, we heard from Dean Fulford, vice-president of Stratford Managers Corp. talked about the impact that a younger cohort of workers on the biotech industry. We’re still on the topic of the 2017 Bio Employee Survey. Janet Le Clair, senior HR consultant for Stratford Managers, will talk about further takeaways from the survey and how Canadian biotech companies can use the survey results to enhance their relationships with employees and further grow their businesses. Listen to what Janet had to say …

In this episode of the Biotechnology Podcast, Dean Fulford, vice-president of HR consulting for Stratford Managers Corp. discusses some key points from the recently concluded 2017 Bio Employee Survey conducted by Biotechnology Focus, Stratford Managers and BioTalent Canada. A younger cohort of employees are making their voices heard, and it will serve biotech companies to listen to their demands, according to Dean.

The results of this year’s Bio Employee Survey are in. And for this week’s episode of the Biotechnology Focus podcast, we’re providing you with an exclusive sneak peek of what the pollsters found. The follow-on poll to Canada’s first-ever biotech and life science HR-focused survey shows encouraging signs regarding the industry’s workplace, according to Dean Fulford, vice president of human resources consulting at Stratford Managers Corp. A few weeks ago, Biotechnology Focus, Stratford Managers, and BioTalent Canada launched the poll in order to take the pulse of the Canadian biotech and life science workplace. This is only the second time such a survey was conducted by the group. The first one in 2015, helped established key benchmarks for the industry. How did the Canadian biotech and life science sector workplace fare this time? Listen to what Dean Fulford has to say……

China’s 3SBio gains a North American through its $290 million purchase of Canada’s Therapure Biopharma Marck’s cladribine tablet Mavenclad achieves sustained control of relapsing multiple sclerosis. A patient enrolled in a CAR-T trial dies. I’m Nestor Arellano. And these are the stories we’ll discuss today on the Biotechnology Focus Podcast. But first, let’s talk about the future of Canada’s life science workplace and workforce +++++ What are the things that employees in Canada’s life science industry value about their workplace? What is it about their organization that keep life science professionals and workers engage and productive each day? How can you, as an employer attract and retain great talent? These are just some of the crucial questions many operators and owners of Canadian life science companies face as they work to grow their business. The key to finding the answers to these questions is data. And the best way to get that data is through the ongoing Biotechnology Focus, Stratford Managers Corporation, and BioTalent Canada nationwide 2017 Life Science Workplace Survey. The poll is one of the most comprehensive attempts to take the pulse Canada’s life science workplace environment. The findings of the survey will provide life science organizations across the country a critical guide on what areas to focus on in order to enhance their operations and relationships with their workers. Don’t miss this chance. There’s still time to take part in the poll. All you have to do is head over to Surveymonkey.com/r/biotechEOS and spend a few minutes taking the poll. Remember that’s surveymonkey.com/r/biotechEOS. Do the survey now and have your say counted. ++++ Early this month, Chinese biotech firm 3SBio Inc., shelled out $290 million For Mississauga, ont’s biologics manufacturer Therapure Biophrama. 3SBio is focused on oncology, nephrology and auto-immune diseases. It has been slowly extending its reach out of its Shenyang headquarters in north China. By purchasing Therapure, 3SBio has effectively put its North American expansion plans into high gear. “3SBio’s global expansion strategy is now on fast track,” according to Dr. Jing Lou, chairman of 3SBio He called the purchase “a key milestone of the global expansion strategy” of his business. The acquisition integrates 3SBio’s mammalian cell culture capabilities and Therapure’s downstream purification and plasma source technologies. This also combines the production capacity of the Chinese company’s recently acquired stakes in Sunshine Guojian Pharmaceutical and Sirton Pharmaceuticals SpA with Therapure’s operations. More than 340 biologics professionals in North America focusing on operations and management, market development, R&D, and manufacturing are expected to join 3SBio. 3SBio will also get certain rights to Therapure’s plasma production and technology, according to the Canadian company. Therapure’s CDMO business will continue to operate under the Therapure brand and be led by Therapure’s CEO Nick Green and the current senior management team at its manufacturing facilities located in Mississauga. +++++ Merck’s Mavenclad branded cladribine tablets for the treatment of highly active relapsing multiple sclerosis has demonstrated the medication a achieve sustained control of the disease over four years with a maximum of only 20 days of oral treatment. The trial, included 806 patients out of 1,184 patients who completed an earlier study. The latest study assessed several clinical efficacy endpoints including annualized relapse rate (ARR) and confirmed three-month Expanded Disability Status Scale (EDSS) progression. ++++ CAR-T therapy has been getting a lot of attention recently. Earlier this month, the FDA gave the green light to Novartis’ CAR-T therapy which uses a patient’s own immune cells to destroy aggressive blood cancer cells. With this method, the patient’s T-cells are collected and sent to a manufacturing centre where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. French biopharmaceutical firm Cellectis was not a fortunate with its own research. The company’s work on an off-the-shelf CAR-T therapy was placed on hold by the United States Food and Drug Administration following the death of one of the patients enrolled in the company’s clinical trial for the therapy. The hold was placed on both UCART123 ongoing Phase 1 studies, respectively in acute myeloid leukemia (AML) and in blastic plas macy toid dend ritic cell neoplasm (BPDCN). A 78-year-old BPDCN male patient received a dose of CD123-targeting CAR-T UCART 123 on August 16. Nine days later, the patient died. Another patient treated in the study experienced a similar but less severe reaction. The 58-year-old woman with AML was given the same dose of UCART 123 as the BPDCN patient. Now Cellectis has to determine what precautions to take before moving forward with enrolling more BPDCN and AML patients for the two phase 1 trials it plans. The (Data Safety Monitoring Board) has recommended lowering the dose of UCART123 in both studies to 4g over 3 days. The French biopharmaceutical firm is now working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123. +++++ That’s all the time we have for today. Thank you very much for listening in and I hope you enjoyed our podcast. This is your host Nestor Arellano Inviting you to join us again next week for more biotech news and views on the Biotechnology Focus Podcast.

In this episode of the Biotechnology Focus podcast, Rob Henderson, the president and CEO of BioTalent Canada, discusses what can be done to avert a life science industry talent shortage and why it is important to take the pulse of the sector's workforce landscape.  Recently, BioTalent Canada has partnered with Biotechnology Focus and Stratford Managers Corporation on a life science HR-focused online survey which is open to Canada's life science professionals and organizations from August 28 to September 15.  Henderson discusses how data from the survey can be used by companies to attract new talent, and enhance workplace conditions and work-life balance to retain existing life science professionals. 

What are the things that employees in Canada’s life sciences sector value about their workplace? What attributes of their organization keep them engage and productive each day? How can you, as an employer attract and retain great talent? How can you, as an employee, let your employee recognize what you need to grow your career, become more productive, and engage in your work? In this episode of the Biotechnology Focus podcast, Deal Fulford, vice-president of human resources consulting for Startford Managers Corporation, talks about the nationwide life sciences HR-focus survey his company is conducting with Biotechnology Focus and BioTalent Canada. The poll is one of the most comprehensive attempts to take the pulse Canada’s life science workplace environment. The findings of survey will provide organizations a critical guide on what areas to focus on in order to enhance their operations and relationships with their workers. Dean explains why is important for Canada’s life science professionals, businesses and organization to take part in the survey and have their voices heard.

  Mario Lebrun, former BIO Quebec managing director passes away, Mylan introduces three generic drugs for HIV, and Shire Pharma’s Onivide has been approved for metastatic adeno carcinoma of the pancreas. In this week’s Biotechnology Focus Podcast, we observe the passing of Mario Lebrun. The former managing director of BIO Quebec succumbed to cancer earlier this month. In other news, Mylan of the Netherlands announced it is rolling out in Canada, three generic drugs for the treating HIV. Shire Pharma Canada ULC said its injectable drug Onivyde has been approved for the treatment of metastatic adeno carcinoma of the pancreas. The read the whole stories, please click on the links below: MARIO LEBRUN FORMER BIO QUEBEC MANAGING DIRECTOR PASSES AWAY MYLAN INTRODUCES THREE HIV DRUGS IN CANADA ONIVYDE APPROVED FOR TREATMENT OF PANCREATIC CANCER: SHIRE PHARMA

The ups and down of an Ontario-based pharma company seeking to develop a solution for the world’s deadly opioid epidemic. A custom DNA nucleotide maker locks in on the problem of CRISP Cas9 off-targets I’m Nestor Arellano. And these are the biotech news we’ll talk about today on the Biotechnology Focus podcast +++ Intellipharmaceutics International of Etobicoke, Ont. was decidedly upbeat when it announced a couple of weeks ago the upcoming review by the FDA of its tamper resistant opioid medication called Rexista. Rexista was product squarely aimed at an unmet need. In recent years, Opioid addiction has become a major problem and growing cause of drug overdose deaths in Canada and the United States. At least 2,458 people were reported to have died in Canada last year due to opioid-related overdose. INtellipharma’s product appeared to promise to turn the tide. Rexista was being positioned as an abuse and alcohol-deterrent . It was a controlled-release oral formulation of oxycodone hydrochloride. A Bioequivalet of Purdue Pharma’s OxyContin. Among other things, Rexista contains a blue dye which would mark those who tamper with or crush the tablet. It also contains a nasal irritant designed to keep the drug from being easily inhaled with the application of heat or an open flame. Wow, the FDA review must have looked like a slam dunk. But a few days later, reports came out that a Los Angeles law firm to investigate Intellipharmaceutics and its company’s officers for possible violation of federal security laws. The complaint, filed by a certain Shawn Shanawaz against Intellipharmaceuticas and two of its executives, alleges that the company and its officers violated Sections 10(b) and 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 by making allegedly false and misleading statements or failed to disclose certain information regarding Rexista. Then another law firm law firm Glancy Prongay & Murray LLP (GPM) of L.A. issued a press release saying that it was looking into reports of alleged misconduct by Intellipharmaceutical executives. The press release indicates that the investigation may have something to do with share prices of Intellipharmaceutical. According to GPM the FDA committees voted that Rexista “had not demonstrated properties that can be expected to deter abuse” by the intravenous means and that there was not enough data to support the company’s claims of the product’s abilities to deter abuse by this means. “On this news, the Company’s share price fell $1.13 per share, or 45.3% on July 27, 2017, thereby injuring investors,” GPM said. The law firm was inviting eople who have purchased Intellipharmaceutics or anyone that may have information or questions about the claims to contact GPM. The company’s CEO had earlier said “We are very pleased with the progress made towards our goal of securing FDA approval of our RexistaTM NDA candidate.” A few days later, Intellipharmaceutics issued a statement saying “its management intends to vigorously defend against the allegations set forth in the complaint.” ++++ The ability to modify the gene of an organism through CRISPR genome editing holds the promise of curing diseases such as cancer and leukemia. However, there are also growing concerns that the innovative gene editing technology could alter regions of the genome which researchers are not targeting. A California-based custom manufacturer of DNA and RNA oligo nucleo tides believes it can lick this problem. The company launched a Cas9 enzyme variant which it said can drastically reduce off-target effects in CRISPR genome editing. Integrated DNA Technologies (IDT) said the Alt-R S.p. HiFi Cas9 Nuclease 3NLS enzyme Ok that’s a mouthful. Let’s just call it variant enzyme. The variant enzyme is a recombinant S Pyogenes Cas9 mutant The company said that when used in gene editing it improves specificity while maintaining a high editing efficiency similar to wild-type Cas9. IN short the variant enzyme is able to cut down off target effects. Why is this important? CRISPR Cas9 editing is not as accurate as we would want it to be. There have been warning from experts that it is possible to cause the editing an unintended gene. For example, genome editing could inadvertently disable a tumour-suppressor gene or activate a cancer-causing gene. Or, consider the possibility of an off-target effect where two different chromosomes are joined in a phenomenon called translocation. Translocation is the cause of chronic myeloid leukemia and other conditions. Yeah. That’s bad news. But IDT’s variant enzyme seems to be right on target. “We performed an unbiased evaluation of several versions of high fidelity Cas9 enzyme in primary human stem cells,” said Dr. Matt Porteus from the Stanford University’s Division of Stem Cell Transplantation and Regenerative Medicine. “We have been very impressed with the characteristics of this new IDT enzyme,” he said. He said that unlike other versions, the variant enzyme consistently achieved high on-target editing activity while having low off-target activity. Porteus was so happy with the results he even said his team intends to use the variant enzyme in future experiments on developing genome editing therapies. If you’re interested to learn more about this story Head over to our site Biotechnologyfocus.ca and click on the story: IDT launches Cas9 enzyme which cuts down CRISPR off-targets +++ Ok folks, that all the time we have for today. I hope you enjoyed the stories we just discussed. This is your host Nestor Arellano Inviting you to joins us again next week for more biotech news and views

Creative Destruction Lab probably conjures up images of exploding beakers and test tubes, or worse a company that demolishes buildings. If you’re a researcher or scientist working on potential new treatment or therapy. If you’re a founder or a fledgling company with IP rights to the next killer technology. And your problem is how to get that product to market. You’ll be interested with what the CDL has to offer. The Creative Destruction Lab is actually an exciting new program that pair startup founders experienced entrepreneurs. The aim is to help innovators transition from science projects to high-growth companies. I had a chance to speak with Ajay Agawal, founder of CDL and he’ll be discussing how the Creative Destruction Lab is helping build successful Canadian biotechnology companies.  

And, that was Dr. Christopher Gemmiti, a regenerative medicine professional, making a pitch before a panel of judges, for his company RedactBio. This was during the Perfect Pitch competition held at the recent Toronto conference The Business of Regenerative Medicine. The conference was a three day event organized by the Commercialization Centre for Regenerative Medicine. Even at the best of days, making a pitch before potential funders can be a daunting, if not un nerving task for any entrepreneur in any industry. But, is there a secret formula for making the perfect pitch? We talked to Michael May, chief executive officer of the CCRM.   I hope you enjoyed this edition of the Biotechnology Focus Podcast.

From September 11th to the 12th this year, Vantage Bio trials will be holding its 2nd annual Canada Talks Pharma conference. The event is an opportunity for professionals in the biotechnology and pharmaceutical industries to get together, exchange views, and learn about innovative ideas, new technologies, and clinical research methods. Biotechnology Focus spoke with Vatche Bartekian, president and founder of Vantage Bio Trials. Vatche told us what's in store for attendees in this year's Canada Talks Pharma. Have a listen to what he had to say....

In this episode of the Biotechnology Podcast, we report of the successful results of Merck’s anacetrapib trials. Dr. Don Stewart, principal of Canadian biotech firm PlantForm discusses why his company is building a laboratory in Brazil. We also take a look at Mississauga’s new life science strategy.

By now, it’s no longer a surprise for anyone that the medical marijuana market in the country is geared for explosive growth. Recently Canada’s national drug development and commercialization centre has partnered with Vancouver’s Aequus Pharmaceuticals Inc., on a research program aimed at establishing pre-clinical safety and efficacy of select cannabinoid-based therapeutics. I had a chance to speak with Gordon McCauley, president and CEO of the  Centre For Drug Research and Development  or CDRD. And he provided Biotechnology Focus with some insights into his organization’s partnership with Aequus. Have a listen to our conversation….  

CRISPR genome editing could hold the key for treating and curing diseases such as cancer, leukemia, and HIV/AIDS. But However, Dr. J. Keith Joung of Massachusetts General Hospital warns there is growing evidence that CRISPR could alter regions of the genome which researchers are not targeting. What are the consequences? The iconic Canadian rock band Tragically Hip is one of the latest investors in the country’s growing medical marijuana market. We’ve got these and more in this episode of the Biotechnology Podcast… Click on these links to read full stories: RESEARCHERS WARNED OF CRISPR OFF-TARGET EFFECTS THREE U OF G GETS GENOMICS RESEARCH GET $10.7-M SUPPORT TRAGICALLY HIP PARTNERS WITH ONTARIO CANNABIS PRODUCER

In this episode of the Biotechnology Focus Radio, Liam Kaufman, co-founder of Winterlight Labs discusses with us how AI is powering his company’s speech-based diagnostic platform. This platform natural speech to detect and monitor dementia, aphasia, and various cognitive conditions. About Winterlight Labs: WinterLight Labs is developing a proprietary AI diagnostic platform that can objectively assess and monitor cognitive health. The company's platform can analyze natural speech to detect and monitor dementia, aphasia, and various cognitive conditions. Using a short one-minute sample of speech, WinterLight can characterize the speaker's cognitive, acoustic and linguistic state, including lexical diversity, syntactic complexity, semantic content, and articulation. Using samples of a person’s speech, WinterLight’s platform analyzes hundreds of linguistic cues and can detect dementia of the Alzheimer type and other conditions with accuracies between 82% and 100%, as reported in our peer-reviewed academic studies.  To find out more, click on this link: http://www.winterlightlabs.com/index.html  

In this episode of the Biotechnology Focus Radio, we discuss the approval in Spain of Merus Lab's Sintrom medication.   Microbiome research firm Commense licenses from the University of British Columbia, a biotherapeutic for preventing childhood asthma.   The McPeak-Sirois Groupo and the Quebec Breast Cancer Foundation launch a program that would boost access to breast cancer research.   And the print and digital edition of the May-June Biotechnology Focus Magazine are out.

  At a recent Mississauga Board of Trade event, we caught up with Canada’s Science Minister, the Hon. Kirsty Duncan. Fresh from her trip to Washington, where she spoke with American scientists and championed the need for greater cross-border collaborative research between Canadian and American scientist, the minister took the time to learn about Mississauga’s new Life Science’s focused development strategy. Ms. Duncan also discussed with Biotechnology Focus why she believes the sector should be in the forefront of Canada’s innovation strategy, her ongoing review of Canada’s science and innovation strategy, and the creation of new science research chair positions. --- That was the Hon. Kirsty Duncan, science minister of Canada, discussing the important roles that the biotechnology and life sciences sectors play in the country’s development, and The review of canada’s science strategy. I hope you enjoyed this week’s show. This is you host, Nestor Arellano, Inviting you to tune in again next week, on the Biotechnology Focus Radio.

Over 1 billion people around the world suffer from "needle phobia." Each year, there are countless people who avoid critical therapies and vaccinations simply because of their fear of hypodermic needles. Vancouver's Microdermics Inc.is determined to change all that with its work on an innovative drug delivery system which promises to be safer, less painful, and more cost-effective than traditional hypodermic needles. In this episode of the Biotechnology Focus Podacst, Rory St. Claire, director of technical operations at Microdermics, talks about the unique features of his company's proposed alternative to a medical tool that has been known to make even grown men cry for more than 160 years.