MESSAGE DU PRÉSIDENT ET CHEF DE LA DIRECTION

par Andrew Casey, BIOTECanada

UN MOMENT HISTORIQUE POUR LA BIOTECHNOLOGIE L’un des piliers centraux du message que diffuse biotecanada pour le secteur est le fait que la population mondiale est sur le point de compter neuf ou dix milliards de personnes, ce qui crée d’énormes pressions sur l’environnement et la planète pour que tout ce monde ait accès à de la nourriture, un logement, des soins et du combustible. Les économies et sociétés de partout doivent revoir leurs méthodes de culture, de fabrication, de soins et de production de combustible. La biotechnologie peut jouer un rôle névralgique en ce sens. Les pays dotés d’un secteur dynamique de la biotechnologie capable de trouver des solutions à ces enjeux bénéficieront d’énormes avantages économiques. Alors que s’intensifient les inquiétudes concernant le variant delta et la difficulté de vacciner une population mondiale pour prévenir l’émergence de nouveaux variants, le Groupe d’experts intergouvernemental sur l’évolution du climat (GIEC) des Nations unies a publié un rapport [en anglais] sur le changement climatique (https://bit.ly/3yo92Ll) qui prévient sans équivoque que le taux de réchauffement actuel transforme le monde en une sorte de grand cargo océanique, c’est-à-dire qu’il faudra déployer d’énormes efforts pour modifier matériellement le cours des choses. De toute évidence, nous sommes engagés dans une voie insoutenable. Il est bon de se rappeler l’ère des dinosaures : à terme, ce n’est pas la planète qui est en danger, mais plutôt notre espèce si nous ne prenons pas urgemment les grands moyens pour réduire notre empreinte écologique. La biotechnologie pourrait se trouver au cœur de la solution à ce problème. L’incidence économique, sociale et sanitaire de la pandémie a certainement fait voir aux décideurs et au public l’importance stratégique d’un secteur national des sciences de la vie et d’une capacité de biofabrication au pays qui sont solides. Les leçons tirées de la pandémie changeront-elles notre façon de réagir au rapport du GIEC? La pandémie n’aurait pas dû nous prendre autant au dépourvu. Bien avant son arrivée, les experts avertissaient les gouvernements de la probabilité concrète d’une pandémie (de fait, notre propre comité de l’industrie des vaccins a pressé le gouvernement à plusieurs reprises de prendre des mesures pour s’y préparer). La plupart des mises en garde sont restées sans écho ou ont à peine fait réagir. En conséquence, quand la pandémie a frappé, les autorités gouvernementales ont été prises de court et ont dû construire l’avion en plein vol. Quelques mois plus tard, il est clair qu’elles n’ont guère envie de revivre la même expérience et qu’elles prennent maintenant d’importantes mesures pour se préparer à de futures pandémies. Le budget fédéral de 2021 a affecté plus de 2 milliards de dollars à la croissance du secteur des sciences de la vie au Canada et au renforcement de la capacité nationale de biofabrication. En plus d’être logique sur le plan des politiques publiques, cette importante décision arrive à point nommé pour propulser la croissance du secteur de la biotechnologie au Canada au-delà de la simple biofabrication en période de crise. Pour éviter la crise environnementale d’envergure pandémique que prévoit le GIEC, il serait logique que tous les pays reconnaissent d’urgence les solutions issues de la biotechnologie et qu’ils y investissent. Lancée au printemps de 2020, l’initiative (lisez le document ici [en anglais]) a été un moteur important pour faire connaître aux stratèges politiques la valeur de tout l’écosystème de la biotechnologie pour le Canada. Cet écosystème est une pierre angulaire. Il est d’envergure nationale et comprend toute une série d’entreprises en phase de démarrage, d’universités, d’incubateurs ou d’accélérateurs, de centres de recherche, d’investisseurs et de multinationales du secteur pharmaceutique et de la biotechnologie. Les gouvernements fédéral et provinciaux ont compris l’importance du secteur pour lutter contre les futurs défis de l’ampleur de ceux de la COVID, pour améliorer le bilan environnemental et pour amorcer la reconstruction économique nécessaire pour l’avenir. En conséquence, ils élaborent des stratégies et investissent pour faire progresser le secteur, mais aussi la position concurrentielle du Canada. Bien que les investissements et les initiatives soient de bon augure, ils ne sont généralement pas liés par une même stratégie. Ainsi, la position concurrentielle du Canada pour attirer des investisseurs étrangers et faire croître le secteur de la biotechnologie du pays s’améliorerait grandement si les gouvernements fédéral et provinciaux formaient un partenariat stratégique avec le secteur pour concerter leurs investissements et leurs politiques. Par ailleurs, la concurrentialité du secteur dans le monde s’améliorerait largement si les gouvernements prenaient des mesures pour moderniser et coordonner la surveillance réglementaire du secteur. En conséquence, le secteur et les pouvoirs publics doivent s’allier dès maintenant dans un esprit constructif en vue d’atteindre des objectifs variés mais connexes qui touchent à l’ensemble du secteur des sciences de la vie. Avec plus de 240 membres représentant tout l’écosystème de la biotechnologie et tous les secteurs des sciences de la vie, y compris les soins de santé, l’agriculture, la fabrication et l’investissement, BIOTECanada continuera de soutenir toutes les initiatives visant à élaborer une stratégie nationale cohérente pour accroître le vaste potentiel de l’ensemble du secteur de la biotechnologie au Canada.

Note : Le présent texte a été rédigé au déclenchement de la campagne électorale.

As its COVID-19 Vaccine Enters Phase 2 Clinical Trials, Entos Pharmaceuticals Sets Its Sights on Cancer, Aging and Rare Diseases

ENTOS PHARMACEUTICALS INC.’S (ENTOS) PROPRIETARY FUSOGENIX DRUG DELIVERY SYSTEM has proven to be a very effective COVID-19 vaccine platform in clinical trials. The Edmonton biotechnology company believes that its DNA delivery platform can be leveraged to make potent COVID-19 vaccines that will make a big difference in the Third World where dangerously low vaccination rates against the global pandemic still prevail.

Entos has two COVID-19 DNA vaccine candidates. The first candidate, encoding the SARS-Cov-2 spike protein, has been successfully steered through a Phase I clinical trial and is now headed on to Phase II.

“It’s very similar in concept to the approved Moderna and Pfizer coronavirus spike vaccines, except it’s made in DNA. That allows us to store it in the regular refrigerator, and our data suggests that it will be effective after a single dose,” says John Lewis, Entos’ co-founder and chief executive officer.

“Fortunately Canadians have been vaccinated broadly already, so the Phase II trial will be conducted abroad, and will look at an expanded cohort of 500 patients to check if we see the same immunogencity after a single dose or two doses,” he adds.

Dr. Lewis notes that a fridge stable, ideally single dose vaccine, will be much easier and compatible with the cold chain available in low and middle income countries around the globe where there is still an enormous need for primary immunization.

Entos’ second candidate is a pan-coronavirus vaccine.

“This is a next generation vaccine that should provide protection against all of the emerging variants, plus potentially other coronaviruses. And so we’re looking at this one as potentially a single shot booster for any of the other approved vaccines that should confer long term pan-coronavirus protection,” explains Dr. Lewis.

“We’ve selected epitopes in that vaccine that are extremely similar among the different coronaviruses that in our preclinical studies have elicited a strong T-cell response, which we think is associated with long-term durability,” he adds.

Entos is hoping to have both vaccines completed in trials by the end of this year, and then ready for approval in early 2022. Entos has also been working closely with its partners such as the Alberta Cell Therapy Manufacturing Centre at the University of Alberta in Edmonton to expand the clinical-grade manufacturing of its Fusogenix platform. In addition to the fight against COVID-19, Entos has a robust therapeutic development pipeline that leverages its next generation genetic medicine delivery system for many other indications such as oncology, age related diseases, and other infectious diseases. Entos recently launched joint venture OncoSenX, which is advancing a solid tumour gene therapy that Dr. Lewis believes will be the first viable gene therapy for cancer. “It is a gene therapy that detects cancer signalling and basically instructs those cells to commit suicide,” he explains. “It looks for cells that have defective P53 signalling, which are present in most cancers, and activates a suicide program to kill those cells.” Entos plans to initiate that trial in early 2022 at the Cross Cancer Institute in Edmonton, and examine how that treatment will work for a First Participant Dosed in Entos’ COVID-19 Vaccine Clinical Trial variety of solid tumours, including prostate, lung, colorectal, and pancreatic. Entos is working with Oisin Biotechnologies of Seattle to employ a very similar technology used to kill cancer cells to also kill senesence cells, which have been widely implicated in various age-related diseases. “Based on our success with the COVID-19 vaccine, we’re also looking at developing other vaccines and therapeutics for infectious disease. I think our next big target will be a pan-flu vaccine,” says Dr. Lewis. Over the longer-term, Entos is “looking at applying our technology to new advanced approaches like gene editing to cure childhood genetic diseases and other rare diseases,” Dr. Lewis adds.

A united approach to the equity, diversity and inclusion challenge

THE CITY OF MISSISSAUGA’S COMMITMENT TO ADVANCING GENDER EQUITY AND DIVERSITY extends far beyond its own workplace. It has committed to supporting an inclusive work environment through a new initiative with the Healthcare Businesswomen’s Association (HBA Canada) focused on the life sciences sector.

“Mississauga is home to Canada’s second-largest life sciences sector, employing 25,000 people. And it’s growing rapidly – we expect the sector to add another 3,000 jobs in just the next four years,” says Jackie O’Connor, Life Sciences Business Consultant at the City of Mississauga Economic Development Office. “We have one of the most diverse populations in the world, with more than half of the city’s residents born outside of Canada. We must focus on inclusive growth and support our companies in building workforces representative of our diverse community.”

HBA Canada is the Canadian Region of an international non-profit dedicated to elevating women into leadership positions in healthcare organizations. They, like the City of Mississauga, are wholly committed to advancing equity and diversity in the workplace.

Acting on their common commitment, the two organizations established the Equity and Diversity Collaborative (EDC), a ground-breaking consortium of 17 healthcare and life sciences companies dedicated to promoting gender equity and diversity initiatives in the workplace. The Collaborative supports companies and Canadian boards striving to achieve gender parity and significant representation of other under-represented groups, including racialized persons, people living with disabilities and members of the LGBTQ2+ community across their organizations.

It does this by facilitating opportunities for its members to connect, share best practices and learn from one another. This concept of industry-wide collaboration, cooperation and consensus has proven to be successful elsewhere. The Gender Parity Collaborative, a group similar to the EDC and based in the US, has demonstrated improved gender representation among its member companies.

“We believe that we have an opportunity and obligation to improve our inclusion and diversity; for our employees, in the way we do business, and in the communities where we operate,” says Nicole Stuart, Country Head HR for GSK. “By volunteering to be a part of this important initiative, I am gaining external insights, best practices, and partnerships to further foster and support GSK’s I&D focus.”

EDC adopted a Plan-Do-Study-Act (PDSA) approach. At the beginning of the year, Executive Sponsors select the priority area to focus on and, through a series of workshops designed as sprints, their ambassadors plan

specific tactics to implement and begin doing this work. Midway through the year, the Collaborative studies the impact of these tactics, adjusts course, and immediately acts upon those adjustments. For its initial year, the EDC chose to focus on recruitment, hiring and transition/ promotion practices.

Adopting the PDSA approach allowed the collaborative to hit the ground running. So did the organizers’ decision to take immediate-action rather than go through a lengthy planning stage. This was critical as “the pace of change is frustrating, especially for those that have been waiting for equity and inclusion for so long,” says Nita Arora, Agility Coach at Roche Canada and Roche EDC Ambassador. “As individuals and organizational leaders, we need to shorten this time by applying our learnings as quickly as possible versus waiting for system and policy to catch up. Small quick shifts can have an enormous impact - learn and apply.”

Their approach is already bearing fruit. One collaborative member is revamping its job descriptions after a workshop revealed significant differences in how they were perceived by various people in the organization. Also, organizations of all sizes are now readily sharing best practices, ideas and experiences. And some smaller companies, unable to access the resources required to best work with underrepresented groups, are using what they’ve learned from other EDC ambassadors.

Andrew Plank, President and General Manager at Roche (Diagnostics), one of the companies participating in the EDC, emphasized a vital but often overlooked quality of equity and diversity – that it is good for both humanity and business. “This intersection is sometimes missed by leaders . . . but it is this balance that brings people to a shared purpose and understanding to propel both individuals and organizations forward. Leaders play an important role in facilitating this work. The key is creating the conditions and environment for people to evolve and move the organization forward in an inclusive way”

“Change begins when we seek to understand,” says Danielle Portnik, Canadian Regional Chair and co-founder of HBA in Canada. “Impact happens when we come together to do something about it.” The EDC will be measuring the outputs of these combined efforts at the end of the year as the first step in identifying the group’s priority for 2022.

Open to working with others to promote diversity and gender equity in your workplace? Visit https://www.thefutureisunlimited. ca/industries/life-sciences/equity-anddiversity/

Victoria Biotech Attempting to Save Eyesight Of Patients With Rare Disease

A VICTORIA-BASED BIOTECHNOLOGY COMPANY IS TRYING TO HALT THE PROGRESSION OF BLINDNESS for people born with a rare eye disease. Oak Bay Biosciences Inc., a 2020 startup, has developed a potential therapy using a patented molecule designed to halt the progression of Stargardt disease.

“The technology is an aptamer that inhibits the catallytic function of Complement Factor D, a critical regulatory enzyme in the alternative complement pathway known to be inappropriately activated in the retinas of Stargardt patients,” explains Oak Bay chief executive officer David Kroeger.

Stargardt is an autosomal recessive, inherited disease leading to progressive blindness that results from mutations in a gene called ABCA4. An individual needs to inherit two copies of the mutated gene to suffer from Stargardt disease, which causes a big blind spot in the middle of the vision, along with some blurriness and peripheral vision.

“The reason for that is the mutation results in the accumulation of some toxic byproducts that are part of the normal visual cycle. Normally your eyes would deal with that, but they can’t because of the mutation in that gene, ABCA4. So what happens is the places where the most light hits is where you become the most blind,” Dr. Kroeger explains.

Stargardt disease can begin anywhere between childhood and young adulthood. About half of cases involve rapid progression where there will be some level of visual impairment within five years of diagnosis. There are many known mutations of ABCA4 that affect this progression rate differently. But within about 20 years of onset, most of the rapid progressors will have reached legal blindness, says Dr. Kroeger.

Oak Bay’s technology is still in the pre-clinical stage, with human trials expected to begin in mid-2023. Oak Bay hopes to receive conditional approval for the use of its molecule in human eye treatments by the U.S. Food and Drug Administration in 2027, perhaps earlier depending on clinical results and the regulatory environment. This molecule would be administered by an ophthalmologist via an intravitreal injection. “One of the major benefits is that we are looking at a dosing interval of once every four months, rather than once a month,” says Dr. Kroeger, who explains that many intravitreal eye injections today need to occur monthly. “Based on the mouse models, we expect this would be more than 90 per cent effective in preventing retinal cell death, so that could extend the time to blindness to 70 years. That would, in some cases, be a definitive treatment if people are living 70 years, plus, without becoming blind,” Dr. Kroeger explains.

Oak Bay’s board of directors and management team is steeped in knowledge and experience.

Dr. Kroeger is an expert in immunology, having trained with some some of Canada’s top immunologists, including Dr. Brad Nelson at the BC Cancer Agency.

Matthew Levy, Oak Bay’s chief scientific advisor, trained with a pioneer of aptamer technology, and is now himself one of the world’s most foremost aptamer experts. Levy initally developed Oak Bay’s aptamer as a faculty member at the Albert Einstein College of Medicine and followed it to a start-up company, Vitrisa Therapeutics in RaleighDurham, N.C.

Oak Bay subsequently acquired that technology.

Director Chris Astle has strength in Finance and Corporate Governance. Board Chairman Erich Mohr heads up translational development. He is also currently the chairman and CEO of Victoria-based MedGenesis Therapeutix Inc., a biopharmaceutical holding company. Director Paul Erickson is co-founder of Victoria-based Axys Group.

Oak Bay Biosciences is currently fundraising via an equity crowdfunding platform, evaluating partnering opportunities, and is seeking potential clinical investigators and patients who may have an interest in collaborating on the Stargardt program. For more information see the website: www.oakbaybio.com.

New Immunomodulatory Cannabinoid Drug Shows Promise in Fight Against COVID-19

CANADIAN BIOPHARMACEUTICAL COMPANY TETRA BIO-PHARMA INC., A GLOBAL LEADER in cannabinoidderived drug discovery and development, will soon be taking its novel injectable cannabinoid drug product, ARDS003, into human clinical trials.

“Everything is poised to go,” says Tetra Bio-Pharma’s Chief Scientific Officer, Melanie Kelly.

“The non-clinical program, including all of the studies required for an investigational new drug product by the U.S FDA and Health Canada, have been completed and Tetra Bio-Pharma has also finished manufacturing of the clinical drug product in order to move forward with its clinical program,” she says.

Prior to the global pandemic, the Ottawa-headquartered Tetra Bio-Pharma, which is publicly listed, was initially targeting the development of an ophthalmic prescription drug to treat an ocular inflammatory condition called uveitis via local delivery to the eye. However, when the COVID-19 pandemic began in 2020, the company repositioned its drug candidate to aggressively develop it as ARDS003, an intravenous medication for systemic treatment of severe COVID-19 patients in a hospital setting.

In moving forward with ARDS003, the company’s leadership took into consideration decades of pre-clinical data supporting the potential of the active pharmaceutical ingredient used in ARDS003 to dampen systemic hyperinflammation. “We had this incredibly robust pre-clinical data in our sepsis models and, given that with COVID-19 we’re essentially talking about a viral sepsis, we thought that our drug would have signficant efficacy for treating the hyperinflammation that drives acute respiratory distress syndrome [ARDS] in severe COVID-19,” Dr. Kelly explains. ARDS003 acts by activating a novel drug target, the type 2 cannabinoid (CB2) receptor, to dampen the body’s inflammatory response. In part, this works by reducing the excessive release of pro-inflammatory mediators that can give rise to a ‘cytokine storm’ which drives the inflammatory stages of sepsis. “There are many advantages of targeting the CB2 receptor. It’s localized very highly to immune cells with relatively low expression in the brain compared to the type 1 cannabinoid (CB1) receptor, which is expressed throughout the brain and the nervous system. That means drugs that activate the CB2 receptor don’t have the same kinds of behavioural [psychoactive] side-effects that you see with non-selective cannabinoid drugs Dr. Melanie Kelly, Tetra Bio-Pharma’s Chief Scientific Officer

that act at the CB1 receptor,” says Dr. Kelly.

Furthermore, because it acts differently than treatments like steroids, there is the potential for synergistic actions when combined with other antiinflammatory drugs, she explains.

Using a drug that not only selectively modulates key immune cells involved in the host response to pathogens, but acts at a target whose expression is also inducible in inflammatory conditions provides excellent potential for treating hyperinflammation. “In that respect I think ARDS003 is a very promising drug candidate,” Dr. Kelly notes.

The active ingredient in ARDS003 is considered a new molecular entity because it has not previously been used in humans. However, published preclinical studies in animals have characterized the effects of this active ingredient in hyperinflammatory disease models with pathological features comparable to those seen in COVID-19 patients. In these studies, treatment resulted in decreased levels of inflammatory mediators (which are responsible for much of the short- and long-term damage seen in inflammatory diseases), reduced tissue damage, and increased likelihood of survival.

Studies conducted by Tetra Bio-Pharma further support pursuing ARDS003 for the treatment of severe inflammation in COVID-19 patients. Findings from these studies include reduced inflammation and pulmonary fibrosis in a mouse model of hyperinflammatory lung injury, and improved daily health scores in an ongoing study evaluating the effects of ARDS003 in mice infected with the virus causing COVID-19. The clinical program involves an adaptative Phase 1 study. “As soon as the trial data from the first cohort of healthy subjects in the Phase Ia has been reviewed and the data safety monitoring board has given approval to proceed, we can move simultaneously with our COVID-19 patient group,” explains Dr. Kelly. Tetra Bio-Pharma’s multicenter Phase 1b trial could enroll COVID-19 patients in four countries, with clinical testing sites planned for Canada, the United States, Brazil, and India. The company may add additional clinical testing sites, depending on the COVID19 situation around the globe when the trial initiates.

“I think there are some real opportunities here that could be taken advantage of with this particular drug,” Dr. Kelly stresses.

Seneca Centre for Innovation in Life Sciences:

Enabling Ontario’s life science industry to advance technologies and products

THE SENECA CENTRE FOR INNOVATION IN LIFE SCIENCES (SCILS), LAUNCHED IN NOVEMBER 2020, plays a key role in supporting innovation within the local life science ecosystem.

SCILS is a collaboration between Seneca’s School of Biological Sciences & Applied Chemistry and Seneca Innovation. Seneca Innovation supports all applied research activities at Seneca. SCILS is one of Seneca’s newest initiatives and is funded by the Natural Sciences & Engineering Research Council of Canada (NSERC).

“SCILS provides the opportunity to exercise our collective academic and industrial strengths in specialized areas, while collaborating with colleagues who bring experience in their own respective fields,” said Dr. Frank Merante, a PhD in biochemistry and a professor and principal scientist with SCILS. “It also enables us to contribute to an array of applied research projects with industry partners, while engaging students in cutting-edge activities.”

Since inception SCILS has worked on nine applied research projects with local small and medium sized life science companies in Ontario, engaging eight faculty principal investigators and 16 student research assistants.

“One of the big advantages of the NSERC support is our ability to expedite requests and engage with industry partners by saying, ‘We can work with you. We can start on this date. We have this amount of funding available,’” said Paola Battiston, Chair, School of Biological Sciences & Applied Chemistry. “It’s nice to be able to get a quick response back to potential partners, avoiding delays.”

Applied research areas of focus at SCILS are life sciences diagnostics and cosmetic science.

SCILS’ life sciences diagnostics expertise supports companies developing products for metabolomics testing, biochemical diagnostics, immunodiagnostics and molecular diagnostics, used both in clinical and industrial settings. Current projects include point-of-care diagnostic tests, such as lateral flow and dipstick assays for testing of foreign pathogens in food, and veterinary testing applications, among others.

“For example, Kenota Health, based in Kitchener, wanted to express recombinant proteins in yeast,” said Tina Perricone, Research Manager, Applied Research, Seneca Innovation. “The resulting work with Seneca will facilitate the production of cost-effective peanut allergy tests.” Cosmetic science projects at SCILS supports companies seeking to develop safe and effective cosmetic products with consumer appeal through novel formulations and analytical testing for quality and stability. Everist Inc., is a Toronto-based venture-backed beauty essentials startup that has developed a patent-pending waterless haircare paste innovation. Seneca is supporting their work to develop an all-natural shampoo and conditioner. “Everist is going to market and seeing great success as an all-natural brand,” said Ms. Perricone.

Barkev Keoshkerian, a Seneca professor and SCILS researcher, notes that as a participant in the applied research program at Seneca, he has had exciting opportunities to engage with innovative smaller companies that require preliminary research to validate their concept.

“Working closely with a company and bringing a product to commercialization is very rewarding,” said Mr. Keoshkerian. “But the most rewarding aspect of these projects is to be a mentor to students, to help them learn about research, apply their learning and see the sparkle in their eyes as they begin to understand their future career potential.”