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 [email protected] . 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 [email protected]. 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 [email protected] 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.