079 | Acknowledging some of the industry’s best

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