Biotechnology Focus April/May 2018

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

Post-antibiotic apocalypse with the

‘Superbug’

INSIDE:

Special Report:

Biologics Companies in Canada – How are we Faring?

Publication Mail Registration Number: 40052410

April/May 2018 VOLUME 21, NUMBER 2

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FEATURES

contents

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Oncolytic virotherapy: unleashing anti-tumour immunity Oncolytic virotherapy is the use of natural or engineered viruses to combat cancer.

(By Ismael Samudio )

April/May 2018 – VOLUME 21 – NUMBER 2

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24

Post-antibiotic apocalypse with the ‘Superbug’

Pharmacogenomics - A New Era in Precision Health Genomics is driving a paradigm shift from a disease-oriented health-care system to one that is more precise, personalized, predictive, preventative and cost effective.

(By Dr. Catalina Lopez-Correa)

20

IP for Ig: Protection for Antibody-based Assets in the Canadian Market and Beyond This article provides a brief overview of IP issues and considerations for those engaged in antibody technologies.

(By Noel Courage and Phil Goldbach)

22

Clinical Trials Ontario: Collaborating to advance health research for a better tomorrow Clinical trials are critical to advancing health care innovations.

(By Susan Marlin )

24

Post-antibiotic apocalypse with the ‘Superbug’ Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi.

(By Michelle Currie)

27

14

SPECIAL REPORT: Biologics Companies in Canada – How are we Faring?

Qvella’s technology set to reduce time to results in microbiology Qvella’s objective is to attain actionable results in clinically relevant time frames that may save a patient in the nick of time with their technology e-lysis treatment technique.

(By Michelle Currie)

In the industry, people are familiar with the stories from ~100 years ago about Canada’s global leadership in the discovery of antitoxins and insulin. But how has the Canadian biologics industry been faring in the 21st century?

(By Robert Merson)

DEPARTMENTS 6

Research news

8

Business corner

31 Calendar of events www.biotechnologyfocus.ca

in every issue 30

The Last Word Holistic public policy in support of Canadian innovation (By Andrew Casey)

April/May 2018 BIOTECHNOLOGY FOCUS 3

PUBLISHER’S note PUBLISHER/ EDITOR-IN-CHIEF Writer CONTRIBUTING WRITERS

Terri Pavelic Michelle Currie Dr. Ismael Samudio

Rob Merson Noel Courage Phil Goldbach Susan Marlin Andrew Casey Dr. Catalina Lopez-Correa

There has been a flourish of activity in the life sciences industry in Canada since the new year – and there has been no sign of it slowing down. The first quarter of 2018 has brought with it fresh funding and partnerships that are exuding excitement for researchers and companies across the board. This issue sheds some light on a few of those ideas and realities that cover some of the riveting research from coast to coast.

Our special report written by Robert Merson delves into biologics companies in Canada; but which are the companies that we should keep an eye out for as the biologicalbased therapeutics are increasingly becoming the treatment options of choice for the serious diseases of today? Read his report: Biologics in Canada – How are we faring?

Noel Courage and Phil Goldbach’s addition following the special report IP for Ig: Protection for Antibody-based Assets in the Canadian Market and Beyond discusses antibodies and obtaining IP rights as they have clearly become a mainstay in the biotechnology industry in Canada and around the world.

As the paradigm shifts from a disease-oriented health care system to one that is more precise and personalised, Dr. Catalina Lopez-Correa walks us through how advancements in technology are making genomics more affordable and accessible then ever before in her article Pharmacogenomics- A New Era in Precision Health.

The rate of cancer has been increasing, leaving it up to researchers and scientists to come up with more innovative ways to stop tumour cells from proliferating. Dr. Ismael Samudio goes in depth about oncolytic viruses and their potential to stimulate the immune system and combat cancer in his piece Oncolytic virotherapy: unleashing antitumour immunity.

Clinical trials are critical to advancing health care innovations, and a lot of emphasis is put onto the location of the trial itself. Therefore, Susan Marlin, president and CEO of Clinical Trials Ontario goes into more detail regarding how we can make this happen in Canada in her article Clinical Trials Ontario: Collaborating to advance health research for a better tomorrow.

Michelle Currie takes us to the not-so-distant future with Dr. Kevin Schwartz in her article Post-antibiotic apocalypse with the ‘Superbug’, describing some possibilities that could potentiate if society does not change its course of action with antibacterial resistance.

Our innovator this issue is Tino Alavie, president and CEO of Qvella, a molecular diagnostics company that is making it their mission to dramatically reduce time to results in microbiology. Their technology utilizes a novel electrical lysing and sample treatment technique called e-lysis that enables direct and fully-automated rapid detection of infectious agents from unenriched biological samples.

Lastly, we have an editorial contribution from Andrew Casey that touches on the 2018 federal budget and how its impact has provided the life sciences economy with significant funding to fuel innovation and research all over the country.

4 BIOTECHNOLOGY FOCUS April/May 2018

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Elena Pankova John R. Jones Melisa Sukhdeo

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EDITORIAL ADVISORY BOARD Barry Gee, CDRD; Christine Beyaert, Roche Canada; Nadine Beauger, IRIC; Peter van der Velden, Lumira Capital; Jason Field, Life Sciences Ontario; John Kelly, KeliRo Company Inc.; Raphael Hofstein, MaRS Innovation; Gail Garland, OBIO; Albert Friesen, Medicure Inc.; Andrew Casey, BIOTECanada; Ulrich Krull, UTM; Peter Pekos, Dalton Pharma Services Biotechnology Focus is published 6 times per year by Promotive Communications Inc. 1-226 Edward Street, Aurora, ON L4G 3S8, Phone 905-727-3875 Fax 905-727-4428 www.biotechnologyfocus.ca E-mail: biotechnology_focus@promotive.net Subscription rate in Canada $35/year; USA $60/year; other countries $100/year. All rights reserved. No part of this publication may be reproduced without written consent. Publications Mail Registration Number: 40052410 Return undeliverable Canadian addresses to: circulation department – 1-226 Edward Street, Aurora, ON L4G 3S8 National Library of Canada ISSN 1486-3138 All opinions expressed herein are those of the contributors and do not necessarily reflect the views of the publisher or any person or organization associated with the magazine.

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Celebrating science, innovation and solutions September 24 – 30, 2018

globalbiotechweek.ca #GBW2018

R&D news Stem Cells: Making disease a thing of the past

Dr. Bernard Thébaud (Photo Credit: The Ottawa Hospital) Stem cells and regenerative medicine have become an exceedingly hot topic in recent years, pushing our knowledge and capabilities of medicine further and farther. It is an exciting area of medicine due to the cells’ ability to regenerate and repair tissue. They are truly quite remarkable, and the work that is being done with them at The Ottawa Hospital is a testament to that.

Dr. Bernard Thébaud, a scientist and neonatologist from The Ottawa Hospital, is focused on understanding the mechanisms of lung development, injury and repair to design treatments for incurable lung diseases.

His lab has an emphasis on the therapeutic potential of stem cells for treating lung diseases in babies.

Bronchopulmonary dysplasia is a lung disease that typically happens to preterm babies that are born at least 12 weeks early.

Their lungs have not fully developed so they are intubated and mechanically ventilated to stay alive, but these life-saving techniques also damage their lungs.

These issues can extend far past childhood and have lifelong consequences. Therefore, it is an extremely critical issue to tackle. So far in Thébaud’s lab, these mesenchymal stromal cells appear to protect or prevent injury in mice and rat models and efforts to 6 BIOTECHNOLOGY FOCUS April/May 2018

translate this therapy into patients are underway.

Around the age of 40, a person’s lung without disease begins to age, but a person with lung disease will experience an earlier onset of aging. Premature babies with interrupted lung growth may be more prone to an early onset of aging while already experiencing a higher risk of asthma. The researchers are attempting to fine tune the use of stem cells to help heal and prevent any lung injury in the short or long-term. The hope is that mainstay treatments will reach such a level that only the tiniest of babies will need to benefit from stem cell therapy.

Hopefully, this research will continue to clinical trials, but Thébaud stresses the importance of designing these with care because this is all still experimental and no one would want to injure a small child.

Stem cells are a fascinating field, and as modern medicine continues to expand at an exponential rate they have the potential to ascertain that various diseases become a thing of the past and allow society to live longer, more fruitful lives.

To see this story online visit https://biotechnologyfocus.ca/stemcells-making-disease-a-thing-of-the-past/

Western University creates a therapy that “fits like a glove” Researchers at Western University have developed custom-fit gloves to help control tremors in patients with Parkinson’s disease.

Not only does this glove help give them some sense of normality again, but it gives them their independence back as well.

Parkinson’s disease is a long-term degenerative disorder of the central nervous system that tends to affect the motor system the most. The disease progresses slowly over time, and is best exemplified through constant shaking and rigidity. Eventually leading to difficulty walking, swallowing problems and other health conditions. Symptoms may vary from patient to patient.

“If you have seen anybody with Parkinson’s that has tremors, they have them in their entire body, but it’s the ones in their fingers that really prevent them from performing the activities of daily living,” says Ana Luisa Trejos, professor of electrical and computer engineering professor at Western University, and lead investigator of the Wearable Biomechatronics Laboratory Group.

The problem with a lot of the devices that are currently on the market is that they restrict movement in general, which still makes the tasks at hand hard to do. In the worst-case scenario, it can even suppress movement at the level of the elbows or wrists that exacerbates the tremors in the fingers.

The design model of the glove uses a system of sensors that track voluntary movements and separates them from involuntary tremors. The gloves will then suppress the tremor to allow fluid motion of movement.

The current prototype glove was created for the left hand of student Yue Zhou, who used 3D printing to design a custom fit.

The team is also working on improving the glove’s hardware to make it more practical to wear, including reducing the size of the glove’s controller and improving its battery system. Once these pieces are all in place, they hope to find commercial partners to bring the gloves to the market.

If effective, this could dramatically change the lives of people living with Parkinson’s disease, allowing them to do daily tasks many people take for granted.

To see this story online visit https://biotechnologyfocus.ca/westernuniversity-creates-a-therapy-that-fitslike-a-glove/

R&D news Breathing life back in: asthma treatment that will change lives There has been substantial research coming out of the woodworks from across the country in so many areas of health. But, when you are living with a disease and finally find that medication which makes you feel like yourself again, there is truly nothing like it.

This was the case for Jennifer Falkiner. She had been diagnosed with asthma in her thirties and that progressed over time to severe asthma. It is only now, participating in an innovative clinical trial for severe uncontrolled asthma with the use of Fasenra – a respiratory biologic – and the research of Dr. Mark Fitzgerald, primary researcher of the study, that her quality of life and her motivation has returned.

The CALIMA trial was one of three pivotal trials to reduce severe exacerbation requiring prednisone and has shown a 50 per cent reduction in patients who had the active treatment in lieu of the placebo. Fasenra is the only respiratory biologic that provides direct, rapid and near-complete depletion of blood eosinophils from the first dose.

Around the world, asthma affects 315 million people, including an estimated 3 million

Jennifer Falkiner, severe uncontrolled asthma patient Canadians. Roughly 250,000 Canadians live with severe, uncontrolled asthma, which can have a debilitating impact on lung function and quality of life.

Many of the current medications also come with countless side effects, that may

deter the people who need the medication from taking it at all. Prednisone, for example, has been known to affect sleeping patterns, weight gain, severe depression, bloody or tarry stools, slow wound healing, dizziness – just to name a few. Fasenra, on the other hand, has had minute reported adverse reactions and is taken every eight weeks after the initial three doses.

Fasenra has been approved by Health Canada and represents a significant milestone for severe eosinophilic asthma patients, finally offering a new treatment option to help manage their condition.

The change for Jennifer has been dramatic. Going from a place where walking in the heat, scents, and the constant fear of the inability to breathe depicted what she could and could not do with her life, to now swim, skate, kayak, and play with her grandkids – she has never looked back.

To see this story online visit https://biotechnologyfocus.ca/breathing-life-back-in-asthma-treatment-thatwill-change-lives/

bereskinparr.com April/May 2018 BIOTECHNOLOGY FOCUS 7

BUSINESS corner Sanofi knocks the socks off Toronto with C$500-M investment French company Sanofi announces one of their largest investments ever in a single building and knocks the socks off the Toronto life sciences community. Sanofi announces that they are investing €350 million (C$500 million) into their Toronto facility to significantly increase capacity to meet the growing demand for pediatric and booster vaccines and demonstrate their commitment to innovation and leadership in global health.

The announcement was held at Sanofi Pasteur’s Canadian headquarters in Toronto and was joined by the Honourable Navdeep Bains, Minister of Innovation, Science and Economic Development, and the Honourable Steven Del Duca, Minister of Economic Development and Growth.

“Canada has a strong legacy in the research and development of vaccines. With this investment, Sanofi is renewing our longstanding commitment to making Canada central in our effort to protect and improve human health across the globe,” says David Loew, executive vice president and head of Sanofi Pasteur. “Vaccines save three million lives every year and this new facility will take us one step closer to a world where no one suffers or dies from a vaccine-preventable disease.”

The new facility will allow Sanofi Pasteur, the vaccines global business unit of Sanofi, to meet the growing demand of five-component acellular pertussis (5-acP) antigen. The building itself is expected to be completed within three to four years, a year or two to get the quality manage-

Zucara secures $3.9-M in non-dilutive funding from The Leona M. and Harry B. Helmsley Charitable Trust

ld Weaver

Zucara Therapeutics Inc., a Torontobased diabetes life sciences company working to advance the first once-daily therapeutic to prevent low blood glucose levels secures US$3.9 million in non-dilutive funding from The Leona M. and Harry B. Helmsley Charitable Trust.

Helmsley will provide the funding to support preclinical advancement of Zucara’s lead drug candidate “ZT-01”, which is focused on the prevention of hypoglycemia in people with Type 1 diabetes (T1D) and other types of insulin-dependent diabetes. The partnership is structured as a program-related investment (PRI) in the form of a loan to Zucara.

The company is now moving forward with GLP toxicology, GMP manufacturing 8 BIOTECHNOLOGY FOCUS April/May 2018

and other Investigational New Drug/Clinical Trial Application enabling activities to bring its lead drug to Phase I clinical trials in 2019.

Preclinical development work will be led by Dr. Richard Liggins, Zucara’s Chief Scientific Officer, who has helped to bring several similar-stage therapeutics to clinical trials. Zucara continues to work closely with The Centre for Drug Research and Development (CDRD) to build and advance its products.

Dangerously low blood glucose, which can lead to unconsciousness or even death, is a frequent challenge for people with T1D and other types of insulin-dependent diabetes. The constant risk of hypoglycemia means that these individuals must monitor and treat low blood glucose levels with fastacting carbohydrates or, in the case of emer-

ment system up and running, and a year or two to do product development and testing. The site will be equipped to produce the antigens used in the diphtheria and tetanus vaccines.

“This project is one of the most important investments for the Sanofi global industrial network,” says Philippe Luscan, executive vice president, Global Industrial Affairs, Sanofi. “It demonstrates our continued commitment to manufacturing excellence and to better serving our vaccines portfolio to people all over the world.”

To see this story online visit https://biotechnologyfocus.ca/sanofiknocks-the-socks-off-toronto-with-c500m-investment/

gency, have a companion inject them with exogenous glucagon. A therapy that restores the body’s ability to prevent hypoglycemia would prevent dangerous hypoglycemic episodes and would improve management of the disease while reducing long-term complications.

Zucara will join other leading institutions in a Helmsley-supported scientific working group focused on understanding and restoring the pancreas’s natural ability to prevent hypoglycemia in individuals with T1D. In this working group investigators study relevant cell types, including alpha and delta cells, and share knowledge to make therapeutic discoveries within an area of research that is historically underappreciated and underfunded.

This new support builds upon more than US$1M in recently announced funding from JDRF International, the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP), The Centre for Drug Research and Development (CDRD) and MaRS Innovation.

This funding continues to support preclinical activities with Dr. Michael Riddell at York University, a Zucara founding scientist, who has accelerated the technology originally discovered by Drs. Mladen Vranic (Banting and Best Diabetes Centre, University of Toronto) and David Coy (Tulane University).

To see this story online visit https://biotechnologyfocus.ca/zucara-funding-helmsley-trust/

BUSINESS corner AbbVie and the International Myeloma Foundation partner up

AbbVie and the International Myeloma Foundation (IMF) announces they have entered into a collaboration to conduct a landmark retrospective chart review study to better understand and help manage multiple myeloma (MM) – the second most common blood cancer.

“There are significant knowledge gaps about multiple myeloma, and among these gaps is the role of genetic mutations in response to treatment, and the related outcomes for patients,” says Brian G.M. Durie,

M.D., IMF chairman. “This study has the potential to provide valuable real-world evidence that can help advance care for patients, and we are proud to join forces with AbbVie to further advance efforts in research and education in multiple myeloma.”

The primary objective of the study is to determine the overall survival of patients with MM and the t(11;14) translocation, which is present in an estimated 16 to 24 percent of FISH-tested MM cases. IMF researchers from at least 30 participating sites across the world will retrospectively review and characterize the outcomes of 1,500 patients with the t(11;14) translocation identified on FISH, making this study one of the largest and most comprehensive MM studies to date.

The secondary objectives include response rates, progression-free survival, time to progression, time to next treatment, duration of responses and overall survival with different regimens among patients with the t(11;14) translocation. Additional secondary objec-

tives include determining prognostic factors for overall survival among MM patients with t(11;14) translocation and to identify the spectrum of co-existing genetic abnormalities among this patient population.

“The partnership with the International Myeloma Foundation underscores our commitment to meaningfully advance the understanding of blood cancers, and continue identifying scientific approaches that have the potential to improve care for patients with multiple myeloma,” says Neil Gallagher, M.D., Ph.D., vice president and head, global oncology development, AbbVie. “We look forward to the findings and to continue strengthening our ongoing research efforts to provide transformative therapies for patients with multiple myeloma and other blood cancers.”

To see this story online visit https://laboratoryfocus.ca/abbvie-andthe-international-myeloma-foundationpartner-up/

RepliCel’s regenerative technology could take the ‘Polar Silk Road’ to China New opportunities are arising at every turn for the regenerative medicine community.

Research is at the tip of the iceberg, but a company in British Columbia isn’t waiting for the ice to melt. RepliCel, a regenerative medicine company, has been developing autologous cell therapies to treat conditions linked to the deficit of healthy cells required for normal function and healing. Their cell therapies are designed to treat chronic tendinosis, UV-damaged or aged skin, and pattern baldness as an alternative method to surgery, pills, and chemicals.

Recently, YOFOTO, one of China’s largest health and wellness companies announced its intention to invest significant financial backing into the company to market RepliCel’s tendon repair and skin rejuvenation products – and they are not the only one – Shiseido, another giant, has been developing RepliCel’s hair regeneration technology for the Asian market.

Last year hit significant milestones for the company with production of the first fully functioning prototypes of their next generation dermal injector that is optimal for the delivery of injectables into the skin. With patents already issued in the United States and in Europe, the functioning prototypes allow RepliCel to display the applications of the device with other potential partners as they move forward at finalising the mold for the commercial-ready devices.

Last year also saw new clinical data produced on all three biologics programs – thinning hair (androgenic alopecia), aging/sundamaged skin, and chronic tendinopathy (Achilles Tendinosis). The phase 1 clinical data demonstrated overwhelming product safety and highly encouraging signals of product efficacy to regrow hair, rejuvenate skin, and regenerate tendon tissue.

In 2013, RepliCel executed a co-development and licensing agreement with Shiseido that covered all of Asia for their hair regeneration program. Now, with the potential for another deal emerging in Greater China, they have real opportunity to leverage these partnerships to be a leader in regenerative

medicine platform across Asia.

It is a very exciting time for RepliCel as they move forward with a CE mark for their device in Europe and their potential expansion in Asia, as well as refining their US strategy for the launch of their dermal injector. With fascinating development projects in queue and continuing to look for the right opportunities, there will be substantial progress that will come from this innovative regenerative medicine company in the near future.

To see this story online visit https://biotechnologyfocus.ca/replicelregenerative-technology-polar-silk-roadchina/ April/May 2018 BIOTECHNOLOGY FOCUS 9

Cancer

| By Ismael Samudio, Ph.D.

Oncolytic virotherapy: unleashing anti-tumour immunity

O

ncolytic virotherapy is the use of natural or engineered viruses to combat cancer. Though sounding somewhat esoteric, this strategy actually relies on commonly found human and animal viral pathogens, often times engineered to increase their safety and anti-tumoural efficacy. Recent evidence indicates that in addition to direct killing of cancer cells, oncolytic viruses (OVs) can potently stimulate the immune system to mount an attack against, and promote lasting immunity against the tumour.1 Intriguingly, a similar effect was described by Dr. William Coley over 100 years ago when he injected Streptococcus pyogenes (live or heat-killed) into post-operative lesions of sarcoma patients – ahead of his time, Coley described a “commotion in the blood” leading to flu-like symptoms that in 40 per cent of patients resulted in an anti-tumour effect.2 Today, we know that this commotion in the blood is mediated by cells from the immune system that evolved over tens of millions of years to recognize danger signals.

What makes tumour cells susceptible to OVs? The answer is yet to be completely elucidated, but our research group and others believe that the inability of cancer cells to stop proliferating and synthesizing proteins is at the root of their susceptibility to OVs. Whereas normal cells that are infected with a virus (or an OV) will stimulate a protective pathway known as the Interferon response (IR) – which leads to inhibition of protein synthesis and cell division in an effort to prevent further virus spread 3, 4 – most cancer cells are incapable of stimulating this pathway with the consequence that the virus will continue to be produced and infect neighbouring cells.5 Nonetheless, some OVs currently in development have been further engineered to reduce their infectious potential towards normal cells and thus increasing their therapeutic potential. For example, the only currently approved OV is a modified herpes

10 BIOTECHNOLOGY FOCUS April/May 2018

simplex virus -1, Talimogene laherparepvec (Imlygic™, Amgen; approved in the US and Europe for the treatment of melanoma in 2015) which was engineered to remove two pathogenicity genes; one that facilitates evasion of the immune system, and another one that promotes survival of infected cells, resulting in a virus that is incapable of reproducing in normal cells (they either die spontaneously or the immune system removes them).6 There are myriad of OVs currently in development. Some are derived from animal

pathogens, such as Vaccinia, Seneca Valley and Newcastle Disease viruses; some are unmodified human pathogens such as Reovirus, or naturally attenuated human pathogens such as Measles and Coxsackievirus; and yet some have been genetically engineered to increase safety or efficacy such as vesicular stomatitis virus (VSV), Maraba (also derived from VSV), herpes virus simplex-1 (HSV-1), and adenovirus amongst many others.7, 8 The clinical evidence to date suggests that response rates are variable, and that only a

Figure 1: Mechanisms by which OV potentiate anti-tumour immunity Antigen generation

OV

Tumor cell

Mφ/DC

“activated” Mφ/DC “primed” CTL

NK

“activated” NK

CTL

In addition to direct oncolysis, various OV (shown are Adenovirus, Vaccinia and herpes simplex virus) can directly stimulate macrophages (Mφ), dendritic cells (DC) and NK cells via various pattern recognition receptors.

Activated Mφ and DC can in turn promote further stimulation of NK cells, and by crosspresenting tumour antigens released form tumour cells lysed by the OV, they can also crossprime cytotoxic T cells (CTL). Primed CTL and activated NK cells can then induce direct anti-tumour effects, and via memory T cell generation establish long-lasting anti-tumour immunity.

Cancer

The scientific community eagerly awaits the results of all the above clinical trials, and while some have started showing encouraging efficacy and toxicity, we may have to wait for a few years for all the data to be properly analyzed in sufficient numbers of patients. subset of patients appear to respond. For instance, a recent report describes that although the Edmonston strain of measles virus was well tolerated, only 1 out of 32 multiple myeloma patients achieved a complete response (and still cancer free, nearly 4 years after the treatment).9 Similarly, pexastimogene devacirepvec; (JX-594, Sillajen), an OV derived from Vaccinia virus, is reported to be well tolerated in clinical trials for pediatric and adult cancers, but has also shown a disappointing response rate 10-12. Even for Imlygic, emerging data suggests that only 10 per cent of treated metastatic melanoma patients attain a durable response and benefits in long term survival 13 . Though enthusiasm may be tempered by these results, recent advances in immunotherapy are thought to be key to unleash the clinical potential of OVs. Interestingly, it has been reported that “killed” Maraba and HSV-1 (by UV inactivation) can elicit potent immune-mediated anti-tumour effects 14, 15 suggesting that direct destruction of tumour cells may not be required for therapeutic efficacy. In fact, viruses that have lost the ability to replicate, yet can stimulate potent anti-tumour immunity may indeed be the safest OV therapeutic. Perhaps, as observed by Coley with his heat-killed bacteria, or as proposed by Dr. Polly Matzinger in her danger hypothesis, it is the molecular “shapes”, not the pathogenic function per se of the virus or the bacteria that alert our immune system to fight 16 – initially by stimulating our innate immune system (a primordial system evolved to combat dangerous pathogens non-specifically), and subsequently by stimulating our adaptive immune system (exquisitely specific to a particular target).

Though the mechanisms remain incompletely understood, they do provide clues as to how best to potentiate OV therapy in a clinically meaningful way.

It is well established that various receptor families expressed in cells of the innate immune system, such as the Toll-like receptors (TLRs), NOD-like receptors, and STING, amongst others, recognize molecular patterns

commonly associated with pathogenic organisms, or infected/compromised cells 17, 18. Via these receptor families (collectively known as pattern recognition receptors), OVs likely stimulate a “fight or flight” response in innate immune cells that can promote immediate anti-tumour effects via macrophages/monocytes and natural killer (NK) cells, and subsequent anti-tumour effects by stimulating priming of T and B cells by antigen presenting cells 19.

Fig. 1 illustrates some of the mechanisms by which OVs potentiate anti-tumour immunity.

Throughout this mechanistic cascade, there are critical points that can be potentiated with currently available immunotherapeutic strategies. For instance, the priming of T cells by antigen presenting cells can be potentiated anti-CTLA4 checkpoint antibodies, whereas the direct anti-tumour effects of NK or T cells can be further unleashed by anti-PD1 (or antiPD-L1) checkpoint antibodies. Theoretically, any of these interventions could potentiate OV-mediated anti-tumour immunity.

Currently, several of the above immunotherapy strategies are being explored in clinical trials in combination with a variety of OVs. For example, various HSV-1 based OVs are being tested in combination with Ipilimumab (anti-CTLA-4) 20, 21 and Nivolumab (PD-1 inhibitor)22, whereas JX-594 is being tested in combination with Ipilimumab 23, Tremelimumab (anti-CTLA-4), and Durvalumab (anti-PD-L1)24.

Moreover, novel OVs engineered to carry and deliver immune stimulator molecules, such as LOAd703 – an adenovirus armed with CD40L and 4-1BBL which potently stimulate innate and adaptive anti-tumour immunity 25 – are also entering clinical testing. OVs have also been armed with the immunostimulatory cytokine GM-CSF (such as JX-594, CG0070, and Imlygic among others) 26, though in retrospect this particular cytokine may have the downside of stimulating pro-tumour myeloid cells 27, which may contribute to reduced clinical efficacy.

In addition to immunostimulatory strategies, OVs are also being tested in combination with chemotherapy and radiotherapy 28. Moreover, OVs engineered to deliver suicide genes that

convert pro-drugs to toxic metabolites, such as TG6002 29 and Toca-511 30, are also being tested clinically with some encouraging results 31, 32, suggesting that OVs could be well positioned to be combined with various small molecules without increasing the risk of damage to healthy tissues. Similarly, an adenovirus expressing the enzyme thymidylate kinase (TK) is being tested in clinical trials in combination with the anti-viral drug ganciclovir 33, 34 – with the premise that infected tumour cells would express TK and convert ganciclovir to the toxic metabolite ganciclovir triphosphate.

Lastly, recent pre-clinical efforts have also identified molecules that may increase OV spread and infectious potential 35-37. Nonetheless, these potentiation strategies carry with them the inherent risk of fomenting OV replication in normal tissues, thus particular attention to safety and tumour selective delivery will be key for their clinical translation.

It is clear that OV therapy has incredible potential, but we are in the early days of testing and implementation. The scientific community eagerly awaits the results of all the above clinical trials, and while some have started showing encouraging efficacy and toxicity, we may have to wait for a few years for all the data to be properly analyzed in sufficient numbers of patients. We believe that identifying the right genetic modifications to OV (i.e. engineering immunostimulatory molecules, suicide genes, etc.), and the proper combinations with small molecules or therapeutic antibodies, will be instrumental to realize the full potential of oncolytic virotherapy.

Ismael Samudio, Ph.D. is the Head of Biologics at The Centre for Drug Research and Development in Vancouver, Canada.

References available on the digital version.

To see this story online visit https://biotechnologyfocus.ca/oncolyticvirotherapy-unleashing-anti-tumour-immunity/ April/May 2018 BIOTECHNOLOGY FOCUS 11

precision medicine

| By Dr. Catalina Lopez-Correa

Pharmacogenomics A New Era in Precision Health Genomics & Precision Health Genomics is driving a paradigm shift from a disease-oriented health-care system to one that is more precise, personalized, predictive, preventative and cost effective.

Advancements in technology are helping make genomics more affordable and accessible than ever before. Likewise, societal attitudes toward genomics in clinical care are shifting. We are no longer asking ‘if’ genomics should be integrated with clinical care.

Instead we are asking ‘when’ and ‘how’ we can use genomics to benefit as many people as possible.

Genomics & the Healthcare System With a vision to advance the use and application of genomics in clinical practice, Genome BC has invested almost $370 million in over 160 research projects. Genomics research is already saving lives and improving health outcomes and disease management for patients touched by cancer, heart disease, autism,

“Advancements in technology are helping make genomics more affordable and accessible than ever before.”

12 BIOTECHNOLOGY FOCUS April/May 2018

precision medicine

epilepsy, rare diseases and other debilitating diseases. As genomics research moves from the bench to the bedside, clinical applications of genomics will affect many areas of medicine over the next 10-20 years, improving disease prevention, diagnosis, and treatment, as well as informing our approaches to wellness, nutrition, and public health.

Genome BC has had a long-standing interest in, and support for, a particular aspect of precision health called pharmacogenomics.

Since 2004 we have invested in a number of projects analyzing the unintended side effects of medication, known as adverse drug reactions (ADRs). The discipline of pharmacogenomics, identifying gene variants that predispose people to serious side effects of medications or that alter the way your body will respond to, or metabolize, certain drugs, is being applied to improve the safety and efficacy of many therapeutics and treatments.

We are funding teams across different levels of research in this critical field: in the hospital alongside clinicians, in the pharmacy and with primary care physicians.

At the hospital level Dr. Bruce Carleton and his team are working to prevent ADRs by developing laboratory tests to predict the likelihood of a childhood cancer patient developing an ADR and tools to incorporate these tests into clinical practice. At the pharmacy level another group, led by Dr. Corey Nislow and the BC Pharmacy Association, has developed a community pharmacistbased approach to pharmacogenomic testing wherein a patient’s saliva is tested for genes that will predict adverse reactions to commonly prescribed drugs. Finally, at the family physician level Dr. Martin Dawes and his multi-disciplinary team of doctors, pharmacists, and epidemiologists have developed TreatGx, a unique medication decision support system. Using the highest levels of evidence, TreatGX identifies personalized medication options for multiple common

conditions. The options are presented to the doctor in an easy-to-read format with helpful information such as dosing instructions, potential adverse reactions, and medication cost comparisons.

Each of these research teams are bringing new understanding to the table, as well as integrating their work for maximum benefit to patients.

The Future of Pharmacogenomics The goal of pharmacogenomics is to improve patient outcomes. In order to implement this tool effectively we must: o Validate the efficacy of genomics applications in day-to-day patient care o Ensure we are increasing value to patients and lowering costs o Identify and provide information related to diagnostic criteria and provide the relevant pharmacogenomics test(s) o Develop guidelines to help clinicians use these tests o Change perceptions for healthcare professionals and patients Genome BC is working closely with the provincial government, universities, clinicians and other stakeholders to advance the clinical use of pharmacogenomics.

A Critical Mass Canada is not the only country working to implement precision health - there is a global effort working towards a common goal.

Momentum is building and there are success stories of clinical implementation of genomics happening in real time around the world.

In BC there has been a critical change in the Hereditary Cancer Screening Program at the BC Cancer Agency because of a gene panel test that enables clinicians to test for more than a dozen of the most common mutations all at once, rather than one-by-one. This test

“Genomics research is already saving lives and improving health outcomes and disease management for patients touched by cancer, heart disease, autism, epilepsy, rare diseases and other debilitating diseases.” enables people to learn what cancers they may develop, how often to have medical follow-ups, what cancer screening to get and whether there are preventive lifestyle factors that might mitigate the risks. Wait times for this test have gone from several months to a few weeks and BC Cancer is even helping other provinces clear their backlog. The hereditary cancer panel is now being reimbursed by the BC provincial government and has been fully integrated in clinical practice.

Clinical practice has begun to incorporate genomics technology and applications. Ultimately physicians will have practice guidelines to best move patients along a treatment pathway that is best suited to their own genetic makeup.

Dr. Catalina Lopez-Correa is the Chief Scientific Officer and Vice President, Sectors at Genome British Columbia.

To see this story online visit https://biotechnologyfocus.ca/ pharmacogenomics-a-new-era-in-precisionhealth/ April/May 2018 BIOTECHNOLOGY FOCUS 13

Special Report:

Biologics Companies in Canada

| By Robert Merson

Biologics Companies in Canada How are we Faring?

We in the industry, are all familiar with the stories from ~100 years ago about Canada’s global leadership in the discovery of antitoxins and insulin. These discoveries fuelled the growth of Connaught Laboratories, to manufacture biological-based therapeutics to treat serious diseases of the day (e.g. diphtheria, diabetes and later polio). But how has the Canadian biologics industry been faring in the 21st century? Which are the companies that we should be watching out for as the biological-based therapeutics are increasingly becoming the treatment options of choice for the serious diseases of today?

Start with a Baseline – What are Biologics?

The biotechnology industry is confusing at the best of times. Despite our best intentions, we all generally use the terms, biotechnology and biosciences to define what we are all doing, but there are chasms of differences in the scientific research and development activities for which we are each engaged.

Pharmaceutical therapeutics can date back thousands of years, with the ancient 14 BIOTECHNOLOGY FOCUS April/May 2018

Egyptians using willow trees as a source of acetylsalicyclic acid (or asprin), and purple foxglove flowers as a source of digitalis (or digoxin). The common factor being that these therapeutics are all chemical entities (or small molecules). While many of the original therapeutic compounds were found in nature, the pharmaceutical industry has evolved to reengineer and synthesize their own novel compounds for development as therapeutic candidates.

The best-known story on the first use of a biological-based therapeutic was during the small pox epidemic in the late 18th century. Edward Jenner observed that milkmaids who had been previously exposed to cowpox had built-up an immunity to smallpox. The term “vaccination” originated from infecting individuals with biological material from the cowpox in order for them to build up an immunity to small pox. While vaccines over the past

Special Report:

Biologics Companies in Canada

two centuries have been the most common biological therapeutic, the industry has evolved to include the engineering and biological synthesis of the larger biological molecules, such as novel proteins, antibodies, and nucleotide products. These biological molecules are synthesized in a cellular environment, requiring biological activity to develop them, in contrast to the more traditional chemical synthesis of small molecules.

The past few decades have further complicated the definition of biological therapeutics, with the introduction of genetic engineering, stem cells, and cellular based therapeutics. These are fields in which Canada is well positioned to play a leading role in the development of next generation therapeutics, but these technologies have not been included in the current assessment of Canada’s biologics landscape. However, their importance still does warrant further exploration on another occasion.

The focus of this assessment is to review the landscape for Canadian companies that are focused on the development of novel biological-based therapeutics, or biologics.

“With the growing proportion of biologic compounds being developed as therapeutic candidates, it’s important that Canada support companies that are developing this category of therapeutics.”

Global Trends

Profiling Canadian Development Stage Biologic Platform / Therapeutic Companies

The pipeline for biologics candidates is growing. A recent Nature Biotechnology article tracked the number of FDA approvals for new drug applications and biological license applications over the past 20 years.

Although there have been variations on the total number of approvals from year to year, the average over the first 10 years (19982007) showed that 15% of the total 280 application approvals were for biologics, compared to the next 10 years (2008-2017) with 29% of the total 327 approvals for biologics. This trend shows a near doubling of the overall percentage of biological therapeutic candidates versus traditional drug applications.

Statista also recently published data on the number of biologics in development (including preclinical stage). Their data shows that as of June 2017, the number of biologics in development is over 2,700, with the majority of candidates in cancer (at 836), followed by rare diseases (at 566).

These data alone highlight a growing trend for development stage companies focused on biologics, and Canada is home to many companies that are contributing to this global trend.

An initial search of the Canadian landscape was conducted through the website biopharmaguy.com and supplemented with additional searches of internet resources by the author. The list of companies profiled was selected based on a determination (using public secondary resources) of whether the company was deemed to have IP related to an underlying biologics development platform, or a biologics therapeutic candidate in development. While the assessment of the industry landscape was extensive, it is acknowledged that there may be additional IP based within the Canadian industry landscape that may have been missed through this search process.

A total of 26 Canadian companies were identified and are profiled in Table 1.

Key metrics of note: • Regional representation: o Over 50% of companies (15) are located in Western Canada, with the majority (10 companies) in British Columbia and an additional 5 companies in Alberta;

o Both Ontario and Quebec have a representative number of companies (5 and 4 respectively); o Halifax and Moncton are each home to one of the companies.

• Underlying IP: o Over 50% of the companies (15) have profiled both a proprietary discovery platform as well as internal biologic candidates; o An additional 10 companies have profiled therapeutic candidates as their underlying IP and one of the companies has profiled solely their discovery platform as their underlying IP. • Development stage and focus: o All 25 companies with therapeutic candidates have ongoing activities at the discovery or preclinical stage of development; o At least 14 of the profiled companies have therapeutic candidates in early clinical development; o Of the candidates in early clinical development, at least 8 companies (over half of those in clinical development) have focused on cancer.

April/May 2018 BIOTECHNOLOGY FOCUS 15

Special Report:

Biologics Companies in Canada

Table 1: Canadian Development Stage Biologic Platform / Therapeutic Companies Location

Primary Source for Company IP

Company

Website

City

Prov Discovery / Discovery / Development Platform Development Platform

AbCellera Biologics

www.abcellera.com

Vancouver

BC

Technology for screening and mapping of natural immune responses

Akshaya Bio

www.akshayabio.com

Edmonton

AB

Chimigen technology platform for developing immunotherapeutic agents and for cellspecific targeted delivery of biologicals including siRNA.

Vaccine candidates including: HCV, HBV, HIV at clinical stage; and additional candidates in preclinical development

Alethia Biotherapeutics www.alethiabio.com

Montreal

QB

Patented discovery platform based on Subtractive Transcription-based Amplification of mRNA (STAR)

Therapeutic candidates for metastatic cancer (pre-clinical) and ovarian & breast cancer (Phase I)

Alpha Cancer Technologies

www.alpha-cancer.com

Toronto

ON

Proprietary recombinant human alpha fetoprotein (AFP) with unique immuno-oncology properties

Lead immunotherapy product in Phase I for multiple indications

Bioasis Technologies

www.bioasis.us

Richmond West

BC

Patented xB3 platform to shuttle neurotherapeutics across the blood brain barrier

In-house development program has preclinical candidates for a few CNS disorders

BriaCell Therapeutics

www.biacell.com

Vancouver

BC

Clinical stage immunotherapeutics for breast cancer

Cyon Therapeutics

www.cyontherapeutics. com

Vancouver

BC

Anitbody candidate for sepsis licensed to Novartis to conduct Phase II trials

www.feldan.ca

Quebec City QB

www.formationbiologics. com

Montreal

QB

Immunobiochem

www.immunobiochem. com

Toronto

ON

Proprietary technology that enables the development of antibody-drug conjugates (ADCs) targeted at intracellular tumor antigens

Two ADC candidates in preclinical development

ImmunoVaccine

www.imvaccine.com

Halifax

NS

Proprietary DevoVax delivery formulation has applications across multiple therapeutic indications

R&D stage to develop inhouse immuno-oncology product candidates

Innovative Targeting Solutions

www.innovativetargeting. Vancouver com

BC

Patented HuTARG technology platform for protein engineering

Multiple candidates from discovery to pre-clinical development

Feldan Therapeutics

Delivery method for proteins and nucleic acids

Four biotherapeutic candidates, with the most advanced ready for Phase II trials

Formation Biologics

16 BIOTECHNOLOGY FOCUS April/May 2018

Currently developing an antibody program, but no lead therapeutic candidates yet

Special Report:

Biologics Companies in Canada

Table 1: Canadian Development Stage Biologic Platform / Therapeutic Companies Location

Primary Source for Company IP

Company

Website

City

Prov Discovery / Discovery / Development Platform Development Platform

MedGenesis Therapeutix

www.medgenesis.com

Victoria

BC

Lead candidate for Parkinson’s disease just completed Phase II

Northern Biologics

www.northernbiologics. com

Toronto

ON

First in class lead antibody targeting Leukemia Inhibiting Factor ready for Phase I; with other candidates in development

Novelogics Biotechnology

www.novelogics.com

Vancouver

BC

Oncolytics Biotech

www.oncolyticsbiotech. com

Calgary

AB

OncoQuest Technologies

www.oncoquestinc.com

Edmonton

AB

Technology platform includes a series of monoclonal antibodies that target several cancer markers

Multiple immuno-therapy candidates in clinical development (Phase I/II)

Parvus Therapeutics

www.parvustherapeutics.ca

Calgary

AB

Navacim platform has the potential to generate multiple unique “First in Class” breakthrough therapeutics for the treatment of autoimmune diseases

Multiple candidates with lead product ready for Phase I

Pascal Biosciences

www.pascalbiosciences. com

Vancouver

BC

Platform to discover and develop targeted agents that enable the body’s own immune system to recognize and attack cancers

Product candidates in development

Promedic Life Sciences

www.prometic.com

Laval

QB

Develops both small molecule and plasma derived therapeutics

Quest Pharmatech

www.questpharmatech. com

Edmonton

AB

Majority owner of OncoQuest, which is developing antibody based immunotherapeutic products for cancer

Soricimed Biopharma

www.soricimed.com

Moncton

NB

Developing first in class peptides and peptide-drug conjugates for cancer; lead product completed Phase Ia

Platform for the discovery and development of monoclonal antibodies that target soluble decoy proteins involved with immune system suppression associated with cancer progression

First in class antibody immunotherapy drug currently focused on multiple myeloma

A first-in-class intravenously delivered immuno-oncolytic virus (IOV) for the treatment of solid tumors and hematological malignancies

April/May 2018 BIOTECHNOLOGY FOCUS 17

Special Report:

Biologics Companies in Canada

Table 1: Canadian Development Stage Biologic Platform / Therapeutic Companies Location

Primary Source for Company IP

Company

Website

City

Prov Discovery / Discovery / Development Platform Development Platform

Therapten Biosciences

www.therapten.com

Kelowna

BC

Turnstone Biologics

www.turnstonebio.com

Ottawa

ON

Engineered biral immunotherapeutic targeting cancer cells

Partnered program in Phase I/II trials, with additional internal programs in pre-clinical development

Vaxil Bio Therapeutics www.vxlbio.com

Toronto

ON

In-silico platform to identify signal peptides domains and their subsequent use as immunotherapeutic products

Pipeline includes antigen specific immunotherapies and signal peptin specific antibodies, with lead product in Phase I/II

Zymeworks

Vancouver

BC

Multiple product candiMultiple proprietary platdates for cancer with lead forms to support biologics discovery and development product in Phase I

www.zymeworks.com

Multiple candidates for anticancer protein therapeutics in early development

“While vaccines over the past two centuries have been the most common biological therapeutic, the industry has evolved to include the engineering and biological synthesis of the larger biological molecules, such as novel proteins, antibodies, and nucleotide products.”

18 BIOTECHNOLOGY FOCUS April/May 2018

Other Key Players in the Canadian Biologics Landscape Beyond the discovery platforms and therapeutics in development, there are other Canadian companies with valuable biologics IP that are also contributors to the Canadian biologics landscape. The companies focused on the development of biologics products for use as research tools or diagnostic kits are also worth highlighting. While there are many Canadian companies involved in biologics development and marketing (e.g. CRO’s and distributors), those we have chosen to highlight are ones that have their own IP related to their novel products or platforms.

An additional 9 companies are highlighted in Table 2. These companies are located in BC, Ontario, and Quebec, and are developers or manufactures of biological products for health.

It is also important to recognize those companies that are currently marketing biological-based therapeutic products worldwide.

Many multinational companies involved in biologics development and marketing have a presence in Canada. These companies bring employment in the sector and more importantly access for Canadians to these novel therapeutics. We celebrate companies like Sanofi Pasteur, which acquired Connaught Laboratories, and has continued to showcase Canada’s global leadership in vaccine development and manufacturing for over 100 years.

Special Report:

Biologics Companies in Canada

Table 2: Canadian Companies Producing Biologics Tools / Kits Location Company

Website

City

Affinity Biologicals

www.affinitybiologicals.com

Ancaster

ON

Anogen

www.anogen.com

Mississauga

ON

Augurex

www.augurex.com

Vancouver

BC

Gallus Immunotech

www.gallusimmunotech.com

Mississauga

ON

IgY Life Sciences

www.igylifesciences.com

Toronto

ON

Immune Biosolutions

www.immunebiosolutions.com

Sherbrooke

QB

ImmunoPrecise

www.immunoprecise.com

Victoria

BC

Microbix

www.microbix.com

Mississauga

ON

MRM Proteomics

www.mrmproteomics.com

Montreal

QB

So Why is it Important for Canada to be a Player in the Biologics Sector?

1

Alignment with the global trends – With the growing proportion of biologic compounds being developed as therapeutic candidates, it’s important that Canada support companies that are developing this category of therapeutics. Biologics are increasingly becoming recognized for their ability to manage or manipulate biological pathways to achieve a desired outcome.

This goes well beyond the ability of chemical compounds to simply turn “on” or “off” certain biochemical functions. The potential for biologic therapeutics has exponentially expanded our ability to treat, manage or even prevent disease.

2

High value products / high value jobs – Biologics as a product are much more complicated to develop, test and manufacture, requiring highly skilled personnel to operate and manage. We have demonstrated a growing number of companies at the development stage, but in order to realize the full economic potential of these companies and novel products, it will be equally important to support the clinical testing and manufacturing capabilities for these companies. Due to the complexity of biologics, they are much more difficult to produce and there is typically an unwillingness to relocate the manufacturing once it has been established. Investment in later

Prov

stage development and manufacturing will help to ensure that these companies continue to grow in Canada, providing highly skilled employment, and the global export of high valued products.

3

Novel treatments for improved health – Biologics are opening the door to new options for treatment that were previously unavailable, or perhaps too toxic.

Many rare disorders, that previously had few treatment options, are also benefiting from biologics candidates. At the end of the day, treatment of disease is our ultimate goal. If we can continue to support this important sector, then Canadians along with other global citizens will have increased access to novel treatment options for previously untreatable diseases.

Concluding Thought Canada is recognized as a global player in the biosciences, but it’s a hard sell when one of our best stories, that we continue to promote, is the 100-year-old discovery and development of insulin as a novel biologic for diabetes. We need more 21st century success stories to promote and showcase to the global community. The good news, as demonstrated, is that we have a growing pipeline of many more biologics stories to tell. Let’s make sure that these companies are supported so that Canada can continue to be recognized as a leading player in novel biologics development.

“Investment in later stage development and manufacturing will help to ensure that these companies continue to grow in Canada, providing highly skilled employment, and the global export of high valued products.”

References: 1. Fresh from the biotech pipeline; Chris Morrison; Nature Biotechnology 36, 131–136 (2018); doi:10.1038/nbt.4068 2. https://www.statista.com/statistics/258152/biologic-medicines-in-development-by-therapeutic-category-2016/ Robert Merson is a Certified Management Consultant and entrepreneur in the life sciences sector. He is an occasional contributor to Biotechnology Focus.

To see this story online visit www.biotechnologyfocus.ca/special-reportbiologics-companies-in-canada-how-are-wefaring

April/May 2018 BIOTECHNOLOGY FOCUS 19

intellectual property

| By Noel Courage and Phil Goldbach

IP for Ig: Protection for Antibody-based Assets in the Canadian Market and Beyond

A

ntibodies (immunoglobulins) and other antibody-derived biologics have become a mainstay of the biotechnology industry, both here in Canada and around the world.

Novel antibodies are continuously being designed, modified, expressed and purified for a number of uses, including as therapeutics, diagnostics, or research tools.

As is the case with other types of life science technologies, intellectual property (IP) rights must be a key consideration for anyone creating new and innovative antibodies or antibody-based applications.

This article provides a brief overview of IP issues and considerations for those engaged in antibody technologies.

20 BIOTECHNOLOGY FOCUS April/May 2018

Understanding IP Rights Surrounding Antibodies As is often the case when discussing IP for technologies, the focus here will be on patents and patent protection. However, it is important to note that patents are not and should not be the only type of IP right considered. Trade secrets can be used to protect certain aspects of antibody manufacturing and production particular to an organization. Trademarks, copyright, and industrial designs can all apply to the marketing, branding and selling of products and/or services in the antibody space.

For innovative antibody-based therapeutics, a particular type of IP right called data protection can provide an extra layer of protection (beyond the scope of discussion in this article).

Patents are a powerful tool for maximizing value in an innovative technology. An issued patent gives the patent holder a monopoly over the claimed invention for a period of twenty years (plus some extension time in certain jurisdictions) from the patent application filing date. As antibody-based technologies have increased dramatically, so has the number of corresponding patent filings. As of the writing of this article, the total number of published patent documents (i.e., patent applications plus issued patents) with claims to antibodies or antibody-based products is around 300,000 globally, and 20,000 in Canada. The number of patent documents published by the Canadian Intellectual Property Office (CIPO) has increased almost every year, with more than 100 per year since 1990 and more than 1,000 since 2012. Out of the total 20,000 or so total patent documents, the vast majority (>95%) originated, and are owned, by organizations based outside of Canada. With regard to regulatory approvals, monoclonal antibodies now comprise a large proportion of Health Canada-approved innovative drugs each year – specifically: 8/36 in 2015, 7/35 in 2016, and 10/35 in 2017. To our knowledge, most or all of these drugs originated from outside Canada. Many of the up-and-coming Canadian companies profiled in the feature article in this edition of Biotechnology Focus follow the types of IP strategies outlined below.

Generally speaking, the strongest patent claims (protection) will focus on the antibody itself, a chemical compound. The claim wording reflects the type of invention, such as an antibody directed against a novel antigen versus against a known antigen. In terms of claiming a novel antibody, functional claims may be available in some patent offices (i.e., claims primarily based on antibody binding properties). Applicants may also claim by reference to the minimally required DNA/ protein sequence needed to maintain a desired function. In most cases, this means claiming a specific set of CDR sequences. This provides protection not only for the full-length

intellectual property

The most valuable patent for such an antibody is likely to be the original one claiming the composition of matter – i.e., the minimally required antibody sequences. antibody, but also for antibody fragments, which can be as small as a single domain antibody, that contain the specified CDR sequences. Applicants usually try to protect some amount of variability within CDR sequences – as in a consensus sequence.

Other types of patent claims may focus on a hybridoma, a therapeutic or diagnostic use, a method of manufacture, or kits containing the antibody. Known antibodies can also form part of a larger claim to a new analytical technique or purification method.

IP considerations for specific antibody applications are now discussed.

Therapeutics A global race is now well underway to create the next big drug in the form of a monoclonal antibody or other antibody-derived compound. In fact, many of the top selling drugs in the world are antibodies against targets such as TNFalpha (for treating autoimmune disorders), as well as PD-1 and CTLA-4 (for cancer immunotherapy). The most valuable patent for such an antibody is likely to be the original one claiming the composition of matter – i.e., the minimally required antibody sequences. The original patent application will usually also contain claims to a therapeutic use. In certain cases, a patent office may still allow claims to antibodies that bind to a specific epitope.

During development of a therapeutic antibody, follow-on patent filings can and should be considered for additional innovative advances such as: altered sequences or post-translational modifications, therapeutic formulations, new indications, or new therapeutic combinations. For any such follow-on patent, the subject matter being claimed must be considered novel and nonobvious by an examining patent office over the original patent and any other previous public disclosure.

Diagnostics As in the case of therapeutics, or any antibody application, the most valuable pat-

ent claims for a new diagnostic antibody would be those directed to the antibody sequences. In the diagnostic space, novel antibodies may be raised against a newly discovered biomarker for a disease state, and a corresponding diagnostic test would involve detection of the biomarker using a standardized method such as an ELISA. Diagnostic claims can thus include those to detection kits, labeled or tagged versions of the antibody, detection methods using the antibody, or methods of diagnosing a particular disease. In many jurisdictions, including Canada and the US, it is becoming a complex challenge to obtain diagnostic method claims when these are alleged to be simple correlations between the measurement of a biomarker and a disease state.

This is not an issue, however, when using inventive antibodies or detection methods.

Research Tools These tend to be the least glamorous type of antibody technologies, but IP considerations are still important. As with other antibody applications, a proper cost-benefit analysis is important when deciding whether to file a patent on a research tool. In this space, enforceability can be a challenge if the tool is primarily to be used by competitors secretly in house, as compared to a research tool to be widely sold in a kit.

Biosimilars and Patent Litigation Recent years has seen a global influx of biosimilar antibodies onto the global market as patents for the first set of blockbuster antibody therapeutics begin to expire. Biosimilars, sometimes referred to as subsequent entry biologics (SEBs), are biologic compounds with the same amino acid sequence as a reference biologic, but are not identical, due to complex alterations that can occur during production – for example, post-translation protein modifications or process-specific protein associated impurities. Legal challenges being brought by innovator manufacturers as well as biosimilar

manufacturers are just now making their way through the courts. Recently, in one of the first rulings of its kind, the Federal Court of Canada upheld a patent directed to a use of an innovative antibody (Janssen’s infliximab antibody, Remicade™) and granted the counterclaim that an infliximab biosimilar (Hospira’s Inflectra™) infringed the patent (Hospira v. Kennedy (2018 FC 259)). The results of a possible appeal, as well as upcoming decisions on other challenges, will provide further guidance regarding the bounds of protection afforded by antibody patents vis-à-vis biosimilar challengers.

Summary Intellectual property protection is key to protecting and commercializing antibody inventions. The global trend is toward increased antibody patent filing and enforcement. Many Canadian innovators are now active in this space and intend to be part of this IP trend.

Noel Courage, Partner at Bereskin & Parr LLP. Phil Goldbach is an intellectual property manager at MaRS Innovation, a not-forprofit organization and commercialization agent for 15 leading Ontario academic institutions.

To see this story online visit https://biotechnologyfocus.ca/ip-for-igprotection-for-antibody-based-assets-in-thecanadian-market-and-beyond/ April/May 2018 BIOTECHNOLOGY FOCUS 21

Clinical Trials

| By Susan Marlin

Clinical Trials Ontario: Collaborating to advance health research for a better tomorrow Clinical trials are critical to advancing health care innovations.

22 BIOTECHNOLOGY FOCUS April/May 2018

C

ompanies and study sponsors around the world think carefully about where to conduct their clinical trials. They consider many factors including quality, efficiency and access to clinical trial expertise and patients.

Jurisdictions around the world realise the value of clinical trials and compete to attract the investment and health care options clinical trials provide.

With support from the Government of Ontario, Clinical Trials Ontario (CTO) was launched in 2012 with the goals of improving the clinical trials environment and making Ontario more competitive in the global clinical trials market place. The launch of CTO underscored the importance of clinical trials in keeping and creating high-value jobs, attracting new and innovative therapies and

providing Ontarians with access to innovative approaches in health care.

With Ontario already a leader in bio-sciences and one of the largest clusters in North America, investing in the clinical trials environment made sense. The strategy for CTO was developed by a diverse group of stakeholders in the clinical trials community from hospitals, universities, research ethics boards and industry – pharmaceutical, biotech and medical device companies. Input from across the community was important in identifying the critical challenges faced by sponsors and researchers as well as effective strategies to improve clinical trials and their conduct. The pillars defined in 2012 continue to guide the work of CTO – streamlining the conduct of clinical trials, engaging patients and the public with clinical trials, and promoting Ontario as a preferred location for clinical trials.

The engagement of the clinical trials community has broadened and deepened since the original strategy was penned and remains core to CTO programming. The top priority

Clinical Trials of CTO was establishing a streamlined system for ethics review. With well over 200 hospitals and about half of all clinical research sites in Canada located in Ontario, the opportunity to gain efficiencies in ethics review was evident.

Over 100 volunteers from the clinical trials community – from Research Ethics Boards (REBs), institutions, research teams and industry—helped design and build CTO Stream.

Launched in 2015, CTO Stream supports a single REB in Ontario in providing initial and ongoing ethics review for multiple research sites across the province.

Unique in Canada in its design and voluntary nature, CTO Stream includes a program for reviewing and qualifying REBs and a province-wide web-based ethics review system. Experts from REBs across the province participate in the REB Qualification program and serve on the REB Council which supports quality improvements and harmonization across the system. The engagement of the clinical trials community has been impressive, with 94 participating institutions across the province and 17 qualified REBs. Well over 600 clinical studies are part of the system with an average anywhere from 2 to 18 sites taking advantage of a single ethics review.

By leveraging a single REB review the time and effort to achieve high-quality ethics review across multiple research sites are substantially reduced. The province wide approval of a clinical trial is completed on average in 78 calendar days. New sites are approved to join these studies on average in less than 2 weeks, with 90 per cent of sites being approved in a month or far less. The potential time and cost savings of the streamlined REB system has been recognized by industry – 62 different industry sponsors have studies in the system. CTO Stream has recently expanded to include customized forms to accept multi-site observational research (e.g. epidemiologic studies or chart reviews) and the use of the system will continue to grow.

The success of CTO Stream exemplifies two key attributes of the clinical trials community in Ontario – a commitment to quality and a spirit of collaboration. These attributes are important as CTO works with the community to shorten clinical trial start-up times. Ontario sites will be come more globally competitive as start up times shorten. Additionally, as activities that are repetitive or add little to no value are reduced both public and industry resources will be used more efficiently. The study “start-up clock” starts when a study protocol arrives at a site and ends when the first participant can be recruited. With a mechanism to streamline research ethics review already in place, CTO’s focus is now on

Ontario’s potential to be a leader in clinical trials within Canada and internationally is deeply routed in the clinical trial capabilities and research and health care resources across the province.

These assets are surrounded by a thriving life sciences community and health innovation sector.

cutting the overall time to study start-up. CTO is working with the community to design and implement a ‘Quick Start Program’. This program will employ a variety of supports and tools to ensure efficient study activation, focussing on the negotiation and finalization of clinical trial budgets and agreements.

Shortening study start-up times and developing a ‘Quick Start Program’ were the focus of a CTO workshop held on March 26th in Toronto titled “No Site Left Behind”. The content of the workshop was partly based on learnings from an industry survey of the challenges sponsors faced in Ontario. The workshop included 130 people from industry, clinical trials sites, and institutions. It was emphasized that although Canada is considered a high-quality and reliable location for clinical trials, other countries have more patient potential. To maximize participation in global clinical trials research, sites must be activated as quickly and efficiently as possible. Workshop participants brainstormed solutions to address challenges in activating trial sites quickly. Ideas ranged from specific strategies and resources, to improving communication, transparency and collaboration between industry and sites.

The 2018 CTO Conference followed the workshop on March 27-28, 2018 and under-

scored how the clinical trials environment is evolving at an accelerated pace. Themes resonating from the conference reflected some of the key opportunities and challenges for Ontario and Canada in the coming years.

Evolving technologies—genomics, AI, big data capabilities—will impact how clinical trials are conducted and how evidence to support health care decisions is generated.

Clinical trials were identified as an essential component of our health care system and patient engagement was recognized as an increasingly important component at all stages of the clinical trials process.

A priority strategic pillar for CTO is engaging patients and the public with clinical trials.

CTO has convened a Patient and Public Advisory Group and works with health charities and patient advocacy groups across the province. Over the next year in partnership with these groups CTO will focus on building resources to help patients and the public be more informed about clinical trials. CTO will also invest in resources to improve clinical trials through patient engagement, and help people find and access clinical trials.

Ontario’s potential to be a leader in clinical trials within Canada and internationally is deeply routed in the clinical trial capabilities and research and health care resources across the province. These assets are surrounded by a thriving life sciences community and health innovation sector. CTO will be working more intensely over the next year to fully understand clinical trial capabilities across the province and partner with organizations within and outside Ontario to attract more clinical trials to Canada and Ontario. To assist new international clinical trial partners, CTO has developed the Industry Concierge Program to help connect companies and study sponsors to researchers, trial sites and resources to advance their clinical trials.

The commitment to quality and the spirit of collaboration is evident everywhere in and around the clinical trials environment in Ontario. Patients and health charities, researchers and clinicians, industry and government, hospitals and universities, and our life science and health innovation sectors—all are focused on improving the quality of clinical trials, treatment options for patients and the economic and social well-being of Ontarians.

Susan Marlin is the president and CEO of Clinical Trials Ontario To see this story online visit https://biotechnologyfocus.ca/clinical-trialsontario-collaborating-to-advance-healthresearch-for-a-better-tomorrow/ April/May 2018 BIOTECHNOLOGY FOCUS 23

Antimicrobial resistance

| By Michelle Currie

Post-antibiotic apocalypse with

the ‘Superbug’

24 BIOTECHNOLOGY FOCUS April/May 2018

E

ver consider a world where surgery was no longer an option? It is the unfortunate truth that if society does not slow the progression rate of antimicrobial resistance, life as we have come to know it will no longer be our future.

Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. Without such means of effective treatment, it will compromise therapies that have been used for decades in healthcare and puts society in a very precarious position. Treatments such as major surgery or chemotherapy may fade into the background.

As we stand on the precipice of a postantibiotic apocalypse, this global concern has researchers all over the world clamouring to find a solution before this issue gets out of hand. Kevin Schwartz, an infection prevention and control and antimicrobial stewardship physician from Public Health Ontario is one of those researchers seeking a strategy.

“Antimicrobial resistance is going to be one of the biggest future challenges and it really threatens the way that we practice medicine,” says Kevin Schwartz, also an assistant professor at the Dalla Lana School of Public Health, University of Toronto. “We take for granted some of the modern advances of technology that we will really jeopardize if the trend of antimicrobial resistance continues.”

Antimicrobial resistance happens when microorganisms change from exposure to antimicrobial drugs. It is a natural process that happens over time, but, unfortunately, that timeline has been accelerated due to the misuse and overuse of antibiotics in people and animals. Whether it stems from prescribing patients’ antibiotics for things such as a cold or flu, or when they are given as growth promoters in animals or used to prevent disease in healthy animals, the truth is that we need to find a solution to contend with these “superbugs” – and fast.

Antimicrobial resistant-microbes are found in people, animals, food, and the environment (water, soil, and air.) They can transfer from person to person, from person to animal and animal to person – that includes food of an animal origin – and is present in every country worldwide.

Antimicrobial resistance “It’s such a huge global overwhelming problem. From hospital settings to nonhospital settings, and we use more antibiotics than we probably need to,” states Schwartz.

“There are a variety of reasons for that. Antibiotics are effective and life-saving, and often patients present with unclear diagnoses so antibiotics are often used to be on the safe side and so we are not missing a potentially treatable illness.”

“So, I think a lot of this stems from that.

Fields of antimicrobial stewardship are trying to develop ways to help physicians and prescribers use the antibiotics more appropriately. There’s probably depending on the study and the area being treated, inappropriately prescribed 30-50 per cent of the time. So, there is lots of room to improve our antibiotic use,” Schwartz adds.

However, there isn’t one strategy that is applicable across all patient settings and types of conditions and there is a lot of variability as to how antimicrobial stewardship can be implemented. For instance, the approach to improving antibiotics is going to be quite different depending on the setting. Some examples would be the difference in the intensive care unit compared to hospitalized

simple measures that can be implemented, such as a study done in the US that monitored how a poster mailed to family doctor clinics and signed by the corresponding physician with the intent to use antibiotics appropriately displayed in the waiting room affected overall usage. The study showed that even this simple measure decreased over-prescribing by 20 per cent.

“We have done something similar in Ontario over the last year, so we partnered with Choosing Wisely Canada, which is an organization to decrease waste and improve healthcare efficiency. So, we sent the poster to about 13,000 doctors in Ontario to hang in their offices for a similar purpose,” Schwartz says.

There are discrepancies in the system across the country, however, about the amount of antibiotics being prescribed by population and contrasting health regions. This could be due to the variance of practice of physicians in different geographical locations. Some prescribe more, while others tend to prescribe less – allocating education and feedback as one of the best means to observe overprescribing.

There are notable differences between ur-

“We really take for granted what we now consider a simple condition, where in the past they were life-threatening.

They will become life-threatening again in the absence of effective antibiotics for these problems.”

Dr. Kevin Schwartz.

Photo: Public Health Ontario patients, compared to patients treated in the emergency room, compared to patients treated in family doctor offices.

“My focus is mainly on the out-patient setting,” says Schwartz. “So, how can we approach family physicians and community prescribers to use antibiotics more appropriately?

Some of the strategies to do this would be to provide feedback to family physicians. Some of the stuff that we are scaling up to do is to be able to give doctors some comparisons and feedback. For example, how much antibiotics are they prescribing compared to their peers? Then by identifying those doctors that are high prescribers we can have a significant impact to decrease overall prescribing.”

He goes on to suggest that there are other

ban and rural environments prescription and usage, but through multi-variable modelling incorporating these variables as predictors, it is still undetermined why some prescribe more over others.

“We want to make sure people are using the appropriate medicine for the appropriate condition. So, we’re not using overly broad, overly toxic medication when we do not need to,” comments Schwartz.

A study that was done in the UK highlighted what would happen if the course of action did not change over time. They estimated that there are roughly 700,000 deaths a year from antibiotic resistant infections, and that if we do not do anything by the year 2050, that number could reach a high of 10,000,000. To

put that number in another light, the death toll will surpass cancer and motor accidents combined.

“This is a major global problem that needs a major global response to it. It highlights the important work we need to do in antimicrobial stewardship to improve antibiotic use,” states Schwartz. “It is complicated in that, most antibiotics by weight are used in animals, not in humans, and there’s lots of antibiotics in the environment and in other parts of the population. So, there’s all these different approaches where we need to combine – animal veterinary health with human health with environment – and all these different things need to come together so we can decrease antibiotic exposure and an element of resistance.”

The importance of this issue can not be understated. All the advances that have been accomplished in health care will be for naught if antimicrobial resistance continues down this path. Successfully taking care of premature babies, organ transplant, bone marrow transplant, and complex cancer therapies are all prime examples of procedures that will become incredibly difficult or impossible to achieve. They all rely on the fact that we can treat the complications that go hand in hand with the procedure – namely infections.

These patients are more susceptible to bacterial infection, and without effective antibiotics the procedure may be too risky.

“I think people don’t really realise the huge impact that the spread of antimicrobial resistance will have on all aspects of healthcare that have been advancing over the last 50 years. It really does threaten the way we live our lives and the way we get looked after in the healthcare system,” says Schwartz. “We think back to the way things were during WWI when there was no antibiotics and even a small wound in battle could be life-threatening or limb-threatening. We really take for granted what we now consider a simple condition, where in the past they were lifethreatening. They will become life-threatening again in the absence of effective antibiotics for these problems.”

Physicians and dentists are examples of prescribers that need to prescribe antibiotics appropriately, and for the public to have an awareness of the risks of taking antibiotics unnecessarily over time. This awareness needs to be spread before the world turns into a post-antibiotic era. Antimicrobial resistance is an inevitable process. The bacteria are alive, and they will evolve to survive.

To see this story online visit https://biotechnologyfocus.ca/post-antibiotic-apocalypse-with-the-superbug/ April/May 2018 BIOTECHNOLOGY FOCUS 25

PERSPECTIVE | BY DON BOCCHINFUSO, ASSOCIATE AND NOEL COURAGE, PARTNER BERESKIN & PARR LLP

GETTING MAXIMUM IP FROM R&D

I

P protection allows creators to gain the full economic benefit of their innovations. This promotes reinvestment in R&D, leading to further innovation. For many companies, a strong IP portfolio covering key markets is their most valuable asset. This article demonstrates how different forms of IP can be combined to protect life sciences innovations, using the example of a mass spectrometer.

Patents

A patent grants an exclusive right to manufacture, use, or sell an invention.

In life sciences, patents may be granted on inventions such as new and inventive drug compounds, genetically modified cells, medical devices, methods of synthesis, hardware, and computerimplemented processes. Our mass spectrometer example shows how a single product may be covered by multiple patents. There may be inventions in reagents, chemical processes, mechanics, processors and software.

The entire machine may be patented as a system. A patent may also be granted for an individual component such as a liquid chromatography input. Other patents can cover disposable products, operational processes, assays, and certain processes of analysis. For example, in 2017, Thermo Fisher was granted patents related to a method of operating a mass filter in a mass spectrometry system. In situations where a company decides not to file a patent, keeping an innovation as a trade secret may provide an advantage.

26 BIOTECHNOLOGY FOCUS April/May 2018

Industrial Designs

Industrial designs provide narrow protection on the look (aesthetic) of objects such as shape and pattern. The sleek design of a mass spectrometer casing may be registered. For example, Shimadzu Corporation, has registered the specific ornamental design of its mass spectrometer. An industrial design may even cover simple components such as a sample tube rack. The industrial design can be registered in addition to filing for conventional utility patents on function.

Trademark

Trademark protection grants the exclusive right to use a brand. Like most products, mass spectrometers bear the name or logo of their manufacturer.

This mark serves as a clear indication of the source of the machine, and is a tool used by companies to build and protect goodwill (ie. distinguish their goods or services). “Orbitrap,” “Thermo Fisher,” and “Sciex” are examples of registered trademarks.

Copyright

Copyright grants the exclusive right to reproduce a protected work. Unlike other forms of IP, copyright need not be registered; it exists automatically as soon as work is created (registration does provide additional advantages).

The mass spectrometer itself is not eligible for copyright protection. However, instruction manuals, software code, product images, and laboratory notes are all protected by copyright and

extend IP protection beyond the device itself. Many examples of copyrighted works can be seen on mass spectrometer company websites.

Licensing

IP rights may be economically exploited by way of licensing to others that want permission to use the IP rights. Licences are particularly attractive for companies that do not have the interest or means to profitably exploit an IP right themselves.

Patents covering mass spectrometry innovations have been licensed by significant industry players for both device components and assay methods. As an example, in 2017, SISCAPA Assay Technologies Inc. licensed their mass spectrometry assay calibration technology to Waters Corp.

Litigation

IP litigation enforces IP rights against an infringer. In Canada, a patent owner may seek a permanent injunction preventing an infringer from selling infringing products. A court may also award compensatory damages, or an accounting of profits. An example of patent litigation is the U.S. lawsuit in which Waters Corp paid Applera Corp $18M to settle Applera’s allegations that Waters infringed Applera’s mass spectrometry patent.

Companies should use a wide range of IP tools to protect their innovations, as shown by the mass spectrometer industry. IP supports your own company’s growth and products, but can also be commercially exploited by licensing or enforcement.

innovator

| by Michelle Currie

Qvella’s technology set to reduce time to results in microbiology Tino Alavie President, Co-founder and CEO of Qvella

T

he constant need for speed isn’t just for race car driving or the roadrunner. It is imperative in many aspects of the modern world – including medicine and technology – as society advances towards a more syndicate future.

Qvella, a company from Richmond Hill, Ontario, specialises in molecular diagnostics making it their mission to dramatically reduce the time to results in microbiology.

This objective has the company whizzing to attain actionable results in clinically relevant time frames that may save a patient in the nick of time.

Tino Alavie, president, co-founder and CEO of Qvella, realised that microbiology was still being done in very much the same style as Louis Pasteur – a technology a hundred years old – and that where molecular technology has clearly penetrated virology in bacteriology, it was nowhere to be seen.

Recognising that there was not yet innovation in this category for clinical laboratories, he and four of his colleagues came together

to create Qvella. The aim is to speed up the process of microbiology and develop technologies that would dramatically change the way microbiology was being conducted in clinical settings. Hence, their tagline “Microbiology in minutes”.

“We identified the Achilles heel of microbiology as sample prep,” says Alavie. “It’s very difficult to deal with blood because of two things. One is the background in blood, you have lots of interference, but also because of the scarcity of the pathogens. If you’re looking for pathogens in one millilitre of blood, you have tens if not hundreds of billions of cells – human cells, white blood cells, red blood cells, countless platelets, and just a few pathogenic cells in that sterile fluid. So, it’s a complicated problem because you’re truly looking for a needle in the haystack.”

It is a monumentally challenging task. Traditionally, Louis Pasteur cultured biological fluids so that over time the pathogens and environment would flourish to become detectable and visible and no longer lost in the milieu. However, patients don’t always have the time for that. Time is of the essence in health care.

Tino visited The University of California, Los Angeles (UCLA) to learn of the magnitude of health care problems that surround the industry. Here he was informed of the increasing prevalence in multi-drug resistant pathogens, commonly referred to as ‘Superbugs’ that are learning mechanisms to circumvent the antibiotics. Also that sepsis, an inflammatory response to the presence of an infection is increasing and is the second leading cause of death in hospitals in North

America, while at the same time is the most expensive condition to treat. The confluence of all these problems suggested that there is a very large issue in health care and that it may become worse over time. For altruistic reasons, Alavie and his colleagues created Qvella because this was something they just couldn’t ignore.

“For the first couple years, we were simply solving science problems. It was a science project. We all believed it and believed this was the opportunity,” says Alavie. “So, that was the first two years. Then, as we made progress, we reached out to various government agencies and some angel investors to reach a point where we were able to demonstrate the clinical utility of our alpha prototype in 2015. We were then able to track venture capital institutional investors for a Series A that we closed in late 2015. For the past two years we’ve been productising, and in late 2017 announced the Series B financing and our plan to finish the product manufacturing process and be able to start

“What I find extraordinarily exciting about Qvella is that we are doing something that could change human lives, save human lives.”

April/May 2018 BIOTECHNOLOGY FOCUS 27

Innovator

clinical trials with the final product sometime late 2018.”

The name Qvella is meant to encapsulate all pathogenic cells. So, the “Q” is derived from the idea that in medicine “Q” means everything, and with the company desire to capture what is difficult to capture they took the Spanish form of the word sail, which is “vella” and put the two together. It is analogous to being able to capture all pathogens.

“In the beginning, we faced financing hurdles and being able to do some of the things we wanted to do. So, on the financial side, we had some hurdles attracting money and finding money in Canada. That’s why a huge part of it was self-funded at the beginning.

But finding money in Canada, especially for an in vitro diagnostics company is very difficult,” comments Alavie.

“The other problem we had, because we started out with urine and that’s what we had come to appreciate from UCLA, was quickly learning that the biggest prize and most challenging is blood. Blood is a very difficult sample to deal with. So, when we transitioned from urine to blood our problems in terms of technical difficulty went up by two if not three orders in magnitude, maybe even more,” adds Alavie. “It actually set us back over a year because we had to go back to the drawing board and come up with techniques and methodologies that would enable or lend themselves to being able to process blood samples.”

Qvella’s technology is comprised of two parts – an instrument the size of a printer and a cartridge that contains all the chemistries in wet and dry format that you would need to run the assay. It is a touchscreen system that is fairly simple to use and only takes 60 seconds of your time. Overall, the machine will need to take 45 minutes

28 BIOTECHNOLOGY FOCUS April/May 2018

The aim is to speed up the process of microbiology and develop technologies that would dramatically change the way microbiology was being conducted in clinical settings.

to complete the testing, but it is a step in the right direction to bring results from the bench to the bedside in a shorter duration of time.

“We are now over 60 employees,” says Alavie. “I consider myself an extraordinarily lucky man to be by such intelligent, hardworking people. We’ve been blessed with a pleasant start-up environment because we know the strengths of the various individuals and they know their place in the company and what they need to do, and that functions well together.”

Tino is a serial entrepreneur and has been running companies in various stages of growth for over two decades. Qvella is the fourth company with which he holds the title of CEO. “What I find extraordinarily exciting about Qvella is that we are doing something that could change human lives, save human lives,” says Alavie. “If you look at how antibiotics are administered today and how they are prescribed, it’s always empirically

done because microbiology is simply too late to meaningfully impact treatment decision making. So, the ability to within less than one hour inform clinicians if you have an infection and what type of infection is remarkable. It enables them to a) administer therapy right away, b) start with a tailored therapy, reduce side effect profiles, reducing associated costs, reducing perhaps length of hospitalization and increased mortality, reducing comorbidity, all those things. It’s a very exciting time.”

The technology from Qvella’s lab has the potential to revolutionize the way researchers look at microbiology. Drastically cutting the time for physicians to receive pertinent information, only increases the potential to save a life – and that is what this industry is all about.

To see this story online visit https://biotechnologyfocus.ca/qvellastechnology-set-to-reduce-time-to-results-i n-microbiology/

F

Read it here first.

Canada’s foremost news source on the Canadian life science industry.

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| By Andrew Casey

LAST word

Holistic Public Policy in Support of Canadian Innovation

T

he 2018 federal budget earmarked significant funds to advance science and research; a strong recognition that they are vital building blocks for the Canadian economy. These were welcome steps to solidifying Canada’s reputation as a home to great science and scientific research. But like farming, it is one thing to sow seeds, quite another to grow crops. For the latter, one needs to fertilize, water and tend the field. Similarly, when it comes to research and innovation, the imperative for policymakers and industry alike will be to enhance Canada’s ability to leverage these substantial investments in research to create globally competitive Canadian companies.

If successful in the biotechnology space, Canada can take a leadership role developing solutions for the world and reap the economic benefits in the process.

The Canadian biotechnology sector is a great example of how research, innovation and entrepreneurship within a healthy ecosystem can produce some truly remarkable innovations and companies with enormous potential to fundamentally change how we live our lives and run our economies. The sector is made of nine hundred plus companies which are all moving brilliant ideas from the lab to the real world. The companies are located within geographic clusters which also include as partners research institutes, hospitals, clinical trials and universities. Importantly, these clusters are located in every province across the country with each one having a unique strength and/or focus.

After many long and challenging years of early-stage development, several Canadian biotech stars such as Zymeworks (Vancouver), Aquinox (Vancouver), Northern Biologics (Toronto), and Clementia (Montreal) are poised to take the next step to becoming commercial Canadian companies. New companies such as Blue Rock Therapeutics, Turnstone Biologics, Innovative Targeting Solutions, enGene and others are not far behind while industry incubators and accelerator organizations such as NeoMed, CQDM, Accel-Rx, IRiCor, CDRD are establishing the next wave of companies.

30 BIOTECHNOLOGY FOCUS April/May 2018

The continued collaboration, advancement of established SMEs and emergence of new companies are all very positive signs for the sector and Canada’s economy more broadly. Moreover, the federal government’s commitment to the sector through the Innovation Agenda, Supercluster Initiative, Economic Strategy Table and the federal Budget’s investment in research coupled with similar provincial programs and investments underscore the importance of the sector and will strengthen the ecosystem’s ability to identify and develop the new innovations that represent the next wave of companies. These are very encouraging developments that must be recognized and supported.

However, in the biotech space, it must be recognized that one of the critical components of a healthy biotech ecosystem is the active support and engagement of the large multi-national pharma and biotech companies as they represent very significant partners, investors and adopters for early-stage pre-commercial biotech companies and their innovations. Given the highly specialized nature of health biotech companies and their products, there is a critical connection between the biotech SMEs and the large multi-national companies. Indeed, while the growth of the aforementioned companies is very encouraging, it is important to note that all of these companies have one or more multi-national pharma as an investor and/or partner. Furthermore, the industry incubators and accelerator organizations all rely heavily on the support and partnership of the multi-national companies to drive their work in identifying and launching new Canadian companies.

Recognizing the important catalyst role the multi-national companies currently play and must continue to play in driving Canadian innovation forward, it is vital that government policy in all areas recognize the interconnectivity of all parts of the ecosystem. Public policy that is siloed and solely focused on only saving dollars will ultimately be ineffective and will undermine Canada’s competitiveness and ability to develop innovation. By contrast, holistic public policy which recognizes the interconnectivity of the ecosystem can act to establish positive hosting conditions which greatly enhance Canada’s competitiveness and ability to attract investment and commercialize innovation.

Governments in Canada and elsewhere are all being challenged by the rising costs of healthcare. There are many contributing factors to this challenge. Accordingly, there is no one panacea which will address all of the fiscal challenges and deliver improved healthcare. The truly effective solution will be found in a constructive dialogue involving all stakeholders including industry. Adopting a more holistic approach can ultimately produce sustainable solutions which will support not only greater access and affordability but can also take existing and new investments and programs and turn them into Canadian companies.

Andrew Casey is the president and CEO of BIOTECanada.

To see this story online visit https://biotechnologyfocus.ca/ holistic-public-policy-in-support-of-canadian-innovation/ Got something to say? Please send your comments/letters to biotechnology_focus@promotive.net

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