Biotechnology Focus October/November 2018

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

October/november 2018 VOLUME 21, NUMBER 5

Alzheimer’s There’s still light at the end of the tunnel

INSIDE:

Tackling the Talent Gap in the Cell and Gene Therapy Industry

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FEATURES

contents October/November 2018 – VOLUME 21 – NUMBER 5

10

Bringing up biotech

Biotechnology Focus takes a look at which companies made the top 5 private venture capital financings between 2017-18.

(By Michelle Currie)

13

Tackling the talent gap in the cell and gene therapy industry

To meet increasing demand for newly-approved and upcoming therapies, there is a need to bring more talent into this innovative area of life sciences.

(By Drs. Peter Zandstra and Michael May)

16

Alzheimer’s – There’s still light at the end of the tunnel Alzheimer’s and related dementias are a truly immense problem, and a problem that we cannot afford to ignore any further.

(By Dr. Donald Weaver)

20

MaRS Innovation continues to tighten the Canadian Innovation-based relationship with South-Korea

MaRS Innovation crosses the cultural divide to build a better future for tomorrow.

(By Michelle Currie)

22 How to Evaluate Your Next

Ultra-Low Temperature Freezer Purchase: Caveat Emptor

16

A look at some of the key performance factors when choosing which ultra-low temperature freezer a laboratory should purchase.

(By Steven Lynum)

Alzheimer’s - There’s still light at the end of the tunnel

30

DEPARTMENTS 6

Research news

8

Business corner

31 Calendar of events

6 International study creates urine test that detects tuberculosis in HIV patients www.biotechnologyfocus.ca

Patent Protection for Stem Cells - Expanding Opportunities

Commercializing any therapeutic application is difficult. Careful consideration of patent strategy at the outset of R&D is critical for establishing a competitive advantage.

(By Laurence MacPhie and Donald Bocchinfuso)

in every issue 25

aCROSS CANADA

Riding the biotech current to PEI: Q&A with Rory Francis, PEI BioAlliance (By Michelle Currie)

October/November 2018 BIOTECHNOLOGY FOCUS 3

PUBLISHER’S note PUBLISHER/ EDITOR-IN-CHIEF

Terri Pavelic

Writer

Michelle Currie

CONTRIBUTING WRITERS

Peter Zandstra

Michael May Donald Weaver Steven Lynum Laurence MacPhie Donald Bocchinfuso GRAPHIC DESIGNER CONTROLLER MARKETING MANAGER

As the year moves closer to the fourth quarter, there have been many advancements that will further the life sciences community within Canada and the world. Innovative research is broadening the horizons of medicine and care and expanding the abilities of modern technology.

Canada is a biotech powerhouse with a knowledge-rich talent pool and is a destination for investment capital. With the help of investors, Biotechnology Focus has narrowed down the top 5 private venture capital financings in Michelle Currie’s article Bringing up biotech: Top 5 private venture capital financings between 2017-18.

It is an exciting time for the cell and gene therapy field. To meet the increasing demand for newly-approved and upcoming therapies, we need smart, talented, experienced engineers, scientists and business leaders. Because the industry is still relatively new, there is a shortage of these people. Drs. Peter Zandstra and Michael May discuss this in their article Tackling the talent gap in the cell and gene therapy industry.

Looking into what goes on in the biotechnology sector on Prince Edward Island, Michelle Currie goes in depth with PEI BioAlliance’s executive director, Rory Francis, to give a more eye-opening view of the sector on the maritime province. With the island punching above its weight, check out the article Riding the biotech current to PEI: Q&A with Rory Francis, PEI BioAlliance.

The spectrum of Alzheimer’s is anticipated to only get worse in the coming years ahead.

Sharing his knowledge and expertise on the subject, Dr. Donald Weaver, explains the disease and future possibilities in his article Alzheimer’s – There’s still light at the end of the tunnel.

The world is getting that much smaller as countries expand their reach across the globe, fueling collaboration to stem the gaps in innovation and research. Among those countries seeking opportunities across seas is MaRS Innovation. Read about the collaboration in the article MaRS Innovation continues to tighten the Canadian innovation-based relationship with South Korea.

Choosing the right equipment for your laboratory can be an arduous decision at times.

Steven Lynum helps make this a little bit easier for those seeking an ultra-low temperature freezer. Check out his article How to evaluate your next ultra-low temperature freezer purchase.

Hope you enjoy the read!

Elena Pankova John R. Jones Melisa Sukhdeo

CIRCULATION DIRECTOR David Blondeau circulation@promotivemedia.ca Tel: 905-841-7389

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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R&D news Revolutionary immunotherapy research wages war on cancer Dr. Michele Ardolino (Photo Credit: The Ottawa Hospital)

Immune checkpoint inhibitors are waging a revolutionary war on cancer, but new research challenges the central dogma of how this drug treatment works. This research, published in the prestigious Journal of Clinical Investigation, shows for the first time that often-overlooked immune cells called Natural Killer (NK) cells that play a crucial role in responding to checkpoint inhibitors.

“Checkpoint inhibitors work by waking up the body’s own immune system and unleashing an immune attack on cancer cells,” explains co-senior author Dr. Michele Ardolino, a scientist at The Ottawa Hospital and assistant professor at the University of Ottawa. “For many years, everyone assumed that checkpoint inhibitors targeted immune cells called T-cells. But our research shows that they also target Natural Killer cells and these cells play a key role in the how this treatment works.”

Dr. Arolino led the study together with Dr. David Raulet, a professor at the University of California at Berkeley.

“In the cancer immunotherapy field there has been a singular focus on mobilizing antitumour T-cells, says Dr. Raulet. “We believe that NK cells have an important place at the table. Checkpoint therapy combined with other NK-directed immunotherapies may enable us to target many types of tumours that are currently non-responsive to available therapies.”

T-cells and NK cells can both recognize and kill cancer cells, but they do so in very different ways. NK cells recognize patterns of changes on cancer cells and are the immune system’s first line of defense. A T-cell, on 6 BIOTECHNOLOGY FOCUS October/November 2018

the other hand, recognizes a single abnormal molecule on a cancer cell and initiates a more focused attack.

In the current study, Drs. Ardolino, Raulet and their colleagues investigated the effect of checkpoint inhibitors in various mouse models of cancer. They found that checkpoint inhibitors could shrink tumours even in mice with no anti-cancer T-cells, meaning that some other kind of cell must be responding to the checkpoint inhibitors.

When the mice were depleted of NK cells, it greatly reduced or eliminated the anticancer effect of the checkpoint inhibitors.

They also showed that NK cells produce the same checkpoint receptor molecules that T cells do, inferring they can respond directly to checkpoint inhibitors.

Previously, Dr. Ardolino, worked in Dr. Raulet’s lab in California before he was recruited to The Ottawa Hospital and the University of Ottawa in 2016. Together they are now investigating approaches to further enhance the cancer-killing ability of NK cells.

“My dream is that when people come to the hospital with cancer, we’ll be able to take a biopsy and determine not only the mutations in their cancer, but also profile how their immune system is interacting with their cancer,” says Dr. Ardolino. “Then we would give the patient the immunotherapy treatments that is most likely to work for them.”

To see this story online visit https://biotechnologyfocus.ca/ revolutionary-immunotherapy-researchreveals-wages-war-on-cancer/

International study creates urine test that detects tuberculosis in HIV patients A new way to test for tuberculosis has come to town. Developed in part by University of Alberta researchers, this urine test can detect tuberculosis in people living with HIV earlier and more quickly than before.

Tuberculosis kills millions around the world every year and is the leading cause of death for people living with HIV. It is an infectious disease that mainly affects the lungs and is spread through droplets released into the air by coughs or sneezes. The new urine test will improve the speed and accuracy of diagnosis, providing earlier treatment and improving health outcomes.

“The test works by using an antibody to detect the presence of a carbohydrate produced by the organism that causes tuberculosis,” explains UofA chemist Todd Lowary, who is a collaborator on the project. “Pointof-care tests are important as they can be done in areas where the access to health care is low and comparatively unsophisticated.”

Lowary, an expert in carbohydrate synthesis and the Raymond Lemieux Professor of Carbohydrate Chemistry, was part of an international team, including the Foundation for Innovative New Diagnostics and Fujifilm, that developed the test, called Fujifilm SILVAMP TB LAM.

Todd Lowary (Photo Credit: John Ulan)

“Our contribution was to screen the specificity of a selection of possible antibodies against a panel of different carbohydrates to identify the best one antibody,” says Lowary. “That led to the increased sensitivity of the diagnostic.”

The group has issued a call for trial partners for those who wish to pilot the test in clinical settings. Studies to test the new test’s efficacy with HIV-negative patients and new antibodies are being developed to enhance the test’s performance.

The research was conducted with support from the Alberta Glycomics Centre and the Bill and Melinda Gates Foundation.

To see this story online visit https://biotechnologyfocus.ca/ international-study-creates-a-urine-testthat-detects-tuberculosis-in-hiv-patients/

R&D news Research suggests the gut microbiome may play a bigger role than you think

The word microbiome is becoming more common to hear and may play a bigger role than you think when it comes to your health. New research from scientists at the University of Alberta explore the idea of if the first bacteria introduced into the gut will have a lasting impact and may determine how susceptible one may be to ward off serious chronic diseases.

The findings by UofA microbial ecologist Jens Walter and his colleagues suggest differences in our microbial makeup likely depend on when we acquire our first microorganisms after birth—and the order they arrive in our gut.

The discovery presents an interesting topic of discussion on how these microbiomes—which are as personal as fingerprints—establish themselves and what drives their unique nature. That’s key to figuring out how to change our microbiomes for the better, says Walter.

“Each of us harbours a microbiome that is vastly distinct, even for identical twins. Microbiomes are important for our health, but they appear to be shaped by many unknown factors, so it’s hugely important to understand why we are all different,” he adds.

Studies have already shown that a person’s genetics, diet, environment, lifestyle and physiological state all make small contributions to the variation of the gut microbiome. But those factors account for less than 30 per cent of the variation.

In the study, researchers introduced distinct microbial communities, collected one at a time, from adult mice into the gastrointestinal tracts of young, genetically identical mice. The results showed that the microbiome in the adults was more like the microbiome introduced first.

Even when using a cocktail of four distinct

McGill researchers unearth way to weaken drug-resistant bacteria

types of bacteria, the researchers repeatedly found that the first microbes showed the highest level of persistence and the strongest influence on how the gut microbiome developed.

The discovery about timing brings scientists one step closer to understanding how microbiomes might become disrupted— for example, through caesarean section birth or antibiotic use—which is then more likely to predispose us to chronic diseases, and how to potentially address that.

Poor gut health has been linked to obesity, Type 2 diabetes, heart disease, inflammatory bowel disease, colon cancer, neurological disorders, autism and allergies.

“If we know what drives specific microbiomes in specific people, we can have a much more rational approach to potentially altering the microbiome, and developing strategies to address those diseases,” says Walter. “Having long-term persistence of microbes when they colonize in the gut early in life means that a health-promoting biome could potentially be established by introducing beneficial bacteria straight after birth.”

There are such methods out there— such as some baby formulas spruced up with probiotics—but knowing more about how probiotics affect other members of the gut’s microbial community could bump it up another notch.

“We could be a lot more systematic,” states Walter. “I think in 30 or 40 years we’ll be able to colonize infants with specific bacteria we know are health-promoting and shape the microbiome in a beneficial way.”

Antimicrobial resistance is a growing global issue that threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. To avert this from happening, researchers have been hard at work to unearth solutions – before it’s too late.

Scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) have discovered a new cellular target that can weaken the bacterium Pseudomonas aeruginosa, an intimidating microbe which can become highly tolerant to many antibiotics, and consequently refractory to antibiotic therapy. The team’s findings are published in Proceedings of the National Academy of Sciences (PNAS).

“We identified a new function important to antibiotic tolerance, which could be targeted to enhance the activity of our current antibiotics,” says lead study author Dr. Dao Nguyen, a scientist from the Translational Research in Respiratory Diseases Program at the RI-MUHC and an associate professor of Medicine at McGill University. “This is critical if we want to improve the efficacy of our antibiotics and prevent such treatments from failing.

The Centres for Disease Control and Prevention (CDC) in the United States has listed P. aeruginosa as one of the “nightmare bacteria”, with an impact of roughly 51,000 health care-associated infections each year that results in over 400 possibly preventable deaths. It is a common cause of pneumonia, surgical site infections, bloodstream or urinary tract infections.

The researchers thought that if they inhibit the enzyme activity or the stress signaling system, they could render the pathogen more susceptible to antibiotics; and as it turns out, they were right.

This research that Dr. Nguyen and her team have done may prove to be extremely valuable as the world progresses towards a more drug-resistant future. Without effective antibiotics, the world will be in peril, as treatments such an chemotherapy, invasive surgery, or even a small wound may be jeopardized. This threat requires immediate global action from all government sectors and society.

To see this story online visit https://biotechnologyfocus.ca/research-suggests-the-gut-microbiomemay-play-a-bigger-role-than-you-think/

To see this story online visit https://biotechnologyfocus.ca/mcgillresearchers-unearth-way-to-weakendrug-resistant-bacteria/ October/November 2018 BIOTECHNOLOGY FOCUS 7

BUSINESS corner Feldan Therapeutics closes $12.5-million Series A financing round Feldan Therapeutics closes a $12.5 million Series A financing round led by GC, with the participation of Stonebridge Ventures, a South Korean investor, Anges Québec Capital, including members of Anges Québec, and existing investors. Feldan is focused on the development of its pipeline of therapeutic applications based on the Feldan Shuttle, its proprietary peptide-based intracellular delivery technology.

The platform has been successfully used on several cell types – including human primary cells which are the center of most cell therapies – and allowed the delivery of nucleases, transcription factors, and antibodies. The Shuttle can overcome delivery obstacles in the context of therapeutic use by providing a safe and efficient approach that alleviates manipulation complexity and that is associated with low regulatory burden.

Feldan Therapeutics’ mission is to develop

regenerative medicine therapeutic applications based on the Feldan Shuttle platform.

Feldan Therapeutics has generated a pipeline of clinical applications delineated in two distinct programs, the Natural Killer (NK) cell-based immunotherapy and intracellular antibody delivery, that take advantage of the unique characteristics of the Shuttle.

The Feldan Shuttle enables highly efficient delivery of proteins and peptides inside mammalian cells, both in vivo and ex vivo. Proceeds from the current financing round will support preclinical work that will enable the transfer of the technology to clinical trials.

“Our team is thrilled to work with investors and collaborators who share our belief that intracellular delivery of proteins is the future of medicine,” says Francois-Thomas Michaud, chief executive officer and cofounder of Feldan. “We are also delighted to extend our relationship with key partners

who will support us in bringing the Feldan Shuttle to clinical trial”.

GC is a long-time leader in South Korean public health and is a world-class stakeholder in the biopharmaceutical industry. This strategic investment complements the current collaboration between the GC group and Feldan in the development of NK cell-based therapeutics. “We believe that the Feldan Shuttle has the potential to accelerate the development of next-generation therapies”, says Yong Jun Huh, the chief executive officer of GC. “As a long-term strategic investor, we are very excited to make an investment in this potentially groundbreaking technology and best-in-class management team”.

To see this story online visit https://biotechnologyfocus.ca/feldantherapeutics-closes-12-5-million-series-afinancing-round/

Setting eyes on new heights: CDRD announces first-ever cohort of their Executive Institute CDRD Academy ExecutiveInstitue Group

The Centre for Drug Research and Development, Canada’s national life sciences venture, announces the first cohort of the CDRD Academy’s Executive Institute.

Earlier this year, CDRD and Pfizer Canada announced the launch of the Executive Institute under the umbrella of The CDRD Academy. The Institute is a 10-month, focused executive development program open to a limited number of senior-level life sciences professionals annually. It was made possible by a $1M contribution by Pfizer Canada.

After reviewing dozens of applications from across Canada, the Adjudication Committee has selected a cohort of diverse, talented, and forward-thinking individuals that is gender balanced, and represents a variety of personal and professional backgrounds.

“The core of any business is people and supporting and growing our pool of highly-qualified personnel is critical to drive 8 BIOTECHNOLOGY FOCUS October/November 2018

Canada’s health sciences sector,” says Gordon C. McCauley, president and CEO of CDRD. “Through the CDRD Academy’s Post-Graduate and Undergraduate Institutes, we have seen tremendous success over the past 10 years in helping high-potential scientists be more commercially minded. But, with the addition of the Executive Institute to the CDRD Academy, we are now extending our work to also help high-potential business people lead Canada’s science-based businesses of tomorrow; and ensure Canada has the management talent it needs to lead the life sciences world.”

The CDRD Executive Institute program is delivered in collaboration with the not-forprofit Center for Creative Leadership (CCL).

The program has been custom-designed and aims to combine researched and proven best practices/principles with targeted industry topics to take participants on a leadership journey. It will blend in-depth assessments, workshops, simulations, challenging assignments and executive coaching.

‘’The CDRD Executive Institute is off to a very strong start,’’ says John Helou, president, Pfizer Canada. ‘’This first cohort of life science executives exemplifies the type of leaders needed for the industry to reach its full potential. We are pleased to help meet the development needs expressed by life sciences industry stakeholders across the country, and to be able to count on the leadership of CDRD to implement concrete measures that will increase the innovative skill level of this vital industry. We are confident that the tailored training and coaching will contribute to the success of many life science organizations in Canada, which is critical for the development of new treatments for unmet medical needs’’.

This course offers a unique opportunity that will further the life sciences community within Canada and potentially bring the sector and consequently, the economy to new heights. The first face-to-face session will happen in Vancouver September 12-13, 2018, with additional workshops to be held in Montreal and Toronto throughout the Winter and Spring 2019.

To see this story online visit https://biotechnologyfocus.ca/ setting-eyes-on-new-heights-cdrdannounces-first-ever-cohort-of-theirexecutive-institute/

BUSINESS corner MaRS and UofT to open a new Waterfront Innovation Centre in Toronto

MaRS Discovery District, together with its partner the University of Toronto, are in the final stages of securing a lease with Menkes Developments Ltd. for a new 24,000-squarefoot hub at Toronto’s Waterfront Innovation Centre. Already under construction, the

Waterfront Innovation Centre will create critically needed office space for Toronto’s fast-growing innovation community near the city’s flourishing Discovery District.

“As Toronto becomes a destination for global talent, venture capital and tech corporations, demand for space is at an all-time high.

It’s imperative that we develop new innovative and entrepreneurial hubs in communities across the city,” says Yung Wu, CEO of MaRS. “The Waterfront Innovation Centre is the next destination for the city’s growing innovation sector — one that will further solidify Toronto’s standing as a premier tech centre.”

The Waterfront Innovation Centre is planned to open in 2021 and will be developed by Menkes in partnership with Waterfront Toronto. It will create approximately 400,000 square feet of commercial space and potentially accommodate 3,000 workers.

“The University of Toronto is excited to partner with MaRS to help expand Toronto’s rapidly growing startup scene on the city’s waterfront,” says Meric Gertler, UofT president. “It’s a winning combination — MaRS’s world-class suite of innovation programming and expert support for entrepreneurship with the incredible depth and range at U of T.”

“Toronto is experiencing its lowest commercial vacancy rate ever (three per cent), making the city the most sought after market in North America,” Wu says. “Our startups and partners need more space to scale, and this new development is the ideal location for that growth.”

Designed by Toronto’s Sweeny &Co Architects Inc., the Waterfront Innovation Centre will offer high-speed broadband networking (fuelled in part by self-generating solar power), floor-to-ceiling windows and expansive collaboration spaces. The building is also adjacent to Canada’s Sugar Beach and near Sidewalk Labs’s proposed Quayside neighbourhood.

MaRS will be in the HIVE tower and will provide programming and collaborative working space for scaling startups. The Waterfront Innovation Centre is MaRS and UofT’s second real estate partnership. Their first was the MaRS West Tower in 2015. The 780,000-square-foot tower is more than 99.8 per cent full and is currently home to more than 50 startups, as well as companies such as PayPal, Autodesk and the Vector Institute for Artificial Intelligence.

To see this story online visit https://biotechnologyfocus.ca/marsand-uoft-to-open-a-new-waterfront-innovation-centre-in-toronto/

RepliCel and YOFOTO receive all approvals to complete collaborative investment Vancouver-based RepliCel Life Sciences Inc., a regenerative medicine company developing next-generation technologies in aesthetics and orthopedics, receives the conditional approval required to complete the investment that is part of a previously announced collaboration agreement with YOFOTO focused on commercialization of select RepliCel products in Greater China.

YOFOTO, (China) Health Industry Co. Ltd., has received all the approvals from the Chinese regulatory authorities required to finalize the transaction.

With the required approvals in place, the parties expect to close the investment portion of the Transaction shortly allowing them to then immediately and actively launch their strategic partnership in Greater China (Mainland China, Hong Kong, Macau, and Taiwan) and RepliCel’s next stage of activity outside of Asia.

The investment portion of the Transaction is a CDN $5,090,000 purchase of common shares at CDN $0.95 per share and will include 20 per cent warrant coverage exercisable at CDN $0.95 per share for a period of two years. The deal structure also includes

milestone payments, sales royalties, and a commitment by YOFOTO to finance, over the next five years, the included RepliCel programs and an associated cell processing manufacturing facility in Greater China.

RepliCel believes aesthetic and orthopedic conditions affect approximately one in three people in industrialized nations, including aging/sun-damaged skin, pattern baldness, and chronic tendon degeneration. These conditions, often associated with aging, are caused by a deficit of healthy cells required for normal tissue healing and function.

Additionally, YOFOTO will collaborate with RepliCel on the further development and

commercialization of RepliCel’s tendon regeneration cell therapy (RCT-01), skin rejuvenation cell therapy (RCS-01), and its injection technology for dermal applications (RCI-02) (excluding hair-related treatments) in Greater China.

“This investment represents a positive valuation of RepliCel by a commercially successful company having performed significant due diligence,” states RepliCel president and CEO, R. Lee Buckler. “We are very excited about what we have put in place while awaiting the completion of this transaction. Upon the closing of the investment, shareholders should expect to see RepliCel’s programs and activity gain significant momentum over the coming months with a particular focus on bringing its medical device to market. We will provide shareholders with more details on what this means in a comprehensive update as soon as the transaction has closed.”

To see this story online visit https://biotechnologyfocus.ca/repliceland-yofoto-receive-all-approvals-tocomplete-collaborative-investment/ October/November 2018 BIOTECHNOLOGY FOCUS 9

top 5

| By Michelle Currie

Bringing up Biotech: The top 5 Private Venture Capital Financings between 2017-18

Canada is a biotech powerhouse, consistently at the forefront of change with a strong engine of innovation.

This country has a knowledge-rich talent pool and is a destination for investment capital.

10 BIOTECHNOLOGY FOCUS October/November 2018

B

iotechnology Focus, with the help several investors , has narrowed down the top 5 private venture capital financings in the country within the last couple of years. All these private venture capital companies represent extraordinary advancements in the biotechnology and pharmaceutical space, whose cutting-edge technology has the potential to provide treatment – or even cure – some of the world’s most challenging conditions and diseases.

Listed from the highest grossing financing to the fifth highest overall, these companies have done a tremendous job at raising capital and building a stronger innovation ecosystem that ultimately, will help Canadians and the world across the board.

top 5

1

Repare Therapeutics

Repare Therapeutics takes the cake as the leading private venture capital financing in the last couple of years, taking home a whopping US$68-million in their series A financing round June 22nd, 2017. That money will be used to advance its platform and pipeline of novel medicines that target genetically defined weaknesses of cancers.

The company is developing new, precision oncology drugs for patients that target specific vulnerabilities of tumour cells. Its approach integrates insights from several fields of cell biology including DNA repair and synthetic lethality. Repare’s platform combines a proprietary, high throughput, CRISPR-enabled gene editing target discovery method with high-resolution protein crystallography, computational biology and clinical informatics.

With this financing, Repare emerged from Versant’s Discovery Engines after an 18-month stealth period during which the company advanced its leading CRISPRenabled synthetic lethality drug discovery platform, identified several promising oncology targets and moved multiple programs into preclinical development.

2

Milestone Pharmaceuticals

Runner up was Milestone Pharmaceuticals Inc. pulling a close second on August 1st, 2017. The clinical stage cardiovascular company closed their Series C financing round at US$55-million. The round was led by Novo Holdings A/S and included new investors Forbion Capital Partners and funds managed by Tekla Capital Management, with significant participation from Milestone’s existing investors Domain Associates, Fonds de solidarité FTQ, BDC Capital, Pappas Capital, and GO Capital.

Milestone Pharmaceuticals is a private venture capital-funded cardiovascular drug development company developing new small molecule therapeutics for transient cardiovascular conditions. The company’s lead product, etripamil (MSP-2017), is entering its Phase 3 of development. Etripamil is a potent and short-acting nasally-delivered calcium channel antagonist in development for the episodic treatment of paroxysmal supraventricular tachycardia (PSVT).

The funding will be used to advance etripamil, the company’s lead product, into Phase 3 development including the execution of pivotal and supportive clinical trials, the production of clinical and commercial supplies and pre-launch commercialization activities. The funding will also be used to expand the company’s resources including select additional headcount and advisory support in strategic areas including Marketing and Medical Affairs.

3

Fusion Pharmaceuticals

Taking third place is Fusion Pharmaceuticals on September 25th, 2017 when closing their second Series A financing, for a combined total of US$46-million. New investors in the second closing include Adams Street Partners, Seroba Life Sciences, and Varian Medical Systems Inc., who join the existing group of international investors, FACIT, Genesys Capital, HealthCap, Johnson & Johnson Innovation – JJDC Inc., and TPG Biotech.

Fusion is a clinical stage company and spinout of the Centre for Probe Development and Commercialization (CPDC) focused on developing novel targeted alpha therapeutics for the treatment of chemotherapy resistant cancers. Their first product, FPX-01, combines the precise targeting of a human experienced antibody with Fusion’s linker technology and the alpha emitting cytotoxic isotope Actinium-225 to induce cancer cell death.

FPX-01 is an antibody-targeted radiotherapy, which seeks out a specific biomarker of resistance that is present on nearly all types of treatment refractory cancers. The technology is designed to selectively deliver actinium-225 to tumour cells so that in conjunction with internalisation, the alpha particles emitted will eradicate diseased tissue.

October/November 2018 BIOTECHNOLOGY FOCUS 11

top 5

4

AbCellera Biologics

Coming up as a strong fourth is AbCellera Biologics, a cuttingedge company with leading technology for screening and mapping of natural immune responses. They test antibodies from single B cells at depths of millions of cells per day to unleash the power of natural immunity in the next generation of antibody therapies.

AbCellera Biologics Inc. was awarded a contract from the Defense Advanced Research Projects Agency (DARPA) to develop rapid countermeasures against viral outbreaks March 13th, 2018. Over the four-year contract, AbCellera will receive up to US$30-million in funding to establish an end-to-end platform for rapid pandemic response and will lead an internationally recognized team of experts in virology, antibody discovery, and gene therapy.

The project is part of the Pandemic Prevention Platform (P3), an imperative initiative of DARPA’s Biological Technology Office. The P3 program seeks to develop a robust technology platform for pandemic response capable of developing field-ready medical countermeasures within 60 days of isolation of a viral pathogen. AbCellera’s platform development and testing will include the discovery of thousands of human antibodies against a wide array of influenza strains and validation using a variety of other critical viral pathogens.

5

Fortuna Fix

Just trailing fourth, Fortuna Fix finds themselves in the fifth spot.

Backed by Amgen Ventures, Fortuna Fix secured US$25-million in funding to push its autologous stem cell treatments for Parkinson’s disease and spinal cord injuries into the clinic on November 8th, 2017.

Jan-Eric Ahlfors, CEO and CSO of Fortuna Fix, said in a press statement: “With Fortuna’s technology platform, there finally exists a tremendous opportunity to deliver autologous produced by direct programming (drNPCs) that can readily replace lost neurons, do not require immune suppression, are ethically sourced, efficacious and address some of the largest unmet medical needs by fixing the underlying pathology of cell loss to enable restoration of functionality in patients.”

Fortuna Fix is a next-generation regenerative medicine company focused on neuronal repair and regeneration.

Their vision is to establish regenerative medicine as a new paradigm of health care, bringing real solutions to conditions that cannot be cured by current therapeutic modalities. Fortuna has its eyes set on being the first company to enter the clinic using a patient’s own neural stem cells produced by direct reprogramming to replace lost neuronal tissue due to neurodegeneration and neurotrauma.

To see this story online visit https://biotechnologyfocus.ca/bringing-up-biotech/

bereskinparr.com 12 BIOTECHNOLOGY FOCUS October/November 2018

Talent Gap

| By Drs. Peter Zandstra and Michael May

Tackling

the Talent Gap

in the Cell and Gene Therapy Industry

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or those of us who have been following and working in the cell and gene therapy (CGT) field for a significant number of years, this is an exciting time.

The current global market for regenerative medicine is US$36B and forecasted to grow to reach US$49.41B by 2021. With 977 clinical trials in cell, gene and tissue therapy underway worldwide at the close of the second quarter of 2018 , CGT treatments and regenerative medicine-based technologies have reached a level of momentum that industry,

investors, the health-care system, regulators and the media are taking very seriously.

A “tipping point” has emerged with the seminal approval of Novartis’ Kymriah in the U.S. and Europe, its USD$475,000 list price by the Centers for Medicare & Medicaid Services, and the growing catalogue of highvalue acquisitions in the sector.

To meet the increasing demand for newly-approved and upcoming therapies, there is still a long inventory of challenges to overcome, from manufacturing, supply chain, regulatory, reimbursement, market

accessibility and more. To address these challenges, we need smart, talented, experienced engineers, scientists and business leaders. Because the industry is still relatively new, there is a shortage of these people. To maintain momentum, we need to get serious about training.

Canada’s largest biotechnology company, STEMCELL Technologies, says it has average annual growth of 20 per cent and anticipates hiring 4,000 highly skilled people in science and technology and other professions over the next 10 years.

October/November 2018 BIOTECHNOLOGY FOCUS 13

Talent Gap

“One of the biggest recruitment challenges for STEMCELL is attracting world-class scientific minds with niche training to move from traditional academic jobs into careers in biotechnology.

We are specifically looking for PhD scientists, highly trained in the fields of cell biology, tissue engineering and immunology, to develop new technologies for regenerative medicine and cell-therapy research.” — Dr. Allen Eaves, CEO STEMCELL Technologies

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In a 2016 op/ed in the Vancouver Sun, Dr. Allen Eaves, CEO of STEMCELL Technologies, writes: “One of the biggest recruitment challenges for STEMCELL is attracting worldclass scientific minds with niche training to move from traditional academic jobs into careers in biotechnology. We are specifically looking for PhD scientists, highly trained in the fields of cell biology, tissue engineering and immunology, to develop new technologies for regenerative medicine and cell-therapy research.”

The issue of talent in CGT has at least three bottlenecks: is there the entrepreneurial talent and seasoned management to allow us to scale sucessfully; will there be the necessary specialized skills (cellular and biological engineering, patent law, cell and gene manufacturing, regulatory, reimbursement, etc.) to support this industry; and, are educational institutions offering the interdisciplinary skills to produce the talent that converges in multiple fields of expertise to lead this field moving forward?

Developing entrepreneurial talent, experienced bioengineers and seasoned management happens organically over time and by putting training programs in place. It also happens by leveraging successive wins and cumulative “lessons learned.” The CDRD Life Sciences Executive Institute, in partnership with Pfizer Canada, is an excellent example of a “bottom-up” program designed

to supply Canadian life sciences companies with the executive talent it needs. Rotman School of Management’s Creative Destruction Lab is supporting science-based companies through its mentoring process – we are both advisors – and its new Global Executive MBA for Healthcare and the Life Sciences will give mid- and senior-level executives the business tools and leadership training to help biotech companies to thrive.

The Council of Canadian Academies’ (CCA) 2017 report “Building on Canada’s Strengths in Regenerative Medicine” identified the technical training of highly qualified personnel (HQP) through the Canadian university system as a “strength for regenerative medicine, and more broadly as a strength across many disciplines. […] The recruitment of Canadian HQP with comprehensive technical knowledge by other countries [is] evidence of this strength.” The report points to other reports that support this position, stating that Canada’s “educated and multicultural workforce” is a strength in regenerative medicine.

While Canada graduates very capable scientists and engineers, we need to make the transition to industry smoother for these deeply educated and talented individals. As the CCA report notes, “relevant applied skills could include those related to entrepreneurship, legal and ethical affairs, translational research, clinical trial implementation, prod-

Talent Gap

At the University of Calgary, Professor Michael Kallos is Director of the Biomedical Engineering Graduate Program and Associate Director of the Centre for Bioengineering Research and Education (among other things). He also runs a lab where they are “working on bioprocess development and bioreactor protocols for stem cells, and training bioengineers to design and run them – a critical need!”

uct development, and large-scale manufacturing.” These hybrid skills are already in demand and that will increase as the industry grows.

Biomedical engineering is where engineering design principles and mathematics are applied to medicine and biology, allowing students to make significant contributions to improving human health by finding new diagnostic or therapeutic solutions. This growing discipline is ready-made for CGT. At the University of Calgary, Professor Michael Kallos is Director of the Biomedical Engineering Graduate Program and Associate Director of the Centre for Bioengineering Research and Education (among other things). He also runs a lab where they are “working on bioprocess development and bioreactor protocols for stem cells, and training bioengineers to design and run them – a critical need!”

Many of these university programs will require partnerships with community colleges to train specialized technicians driven by compliance to strict quality systems. The McMaster Mohawk Bachelor of Technology is an example of a program that will supply highly qualified personnel to this sector.

The 55-year-old Institute of Biomaterials and Biomedical Engineering at the University of Toronto has also been graduating highly-trained students who are primed to make an impact in CGT. This model is being refined and built upon in Vancouver where, in 2017, the University of British Columbia (UBC) launched the School of Biomedical Engineering.

As Canada’s first multi-faculty comprehensive biomedical engineering school, UBC is investing in the future by educating the bioengineering talent with in-depth biology deconstructed with quantitative engineering design principles and contextualized with real world health problems. In September 2018, BME@UBC will welcome its first cohorts of undergraduate students, complementing strong and well-established graduate education programs. UBC undergraduate students will be eligible to participate in industry co-op programs during their education.

Beyond education, hands-on experience provided by industry is essential. CCRM, through its advanced manufacturing centre – the Centre for Advanced Therapeutic Cell Technologies – and its new Good Manufacturing Practices facility – the Centre for Cell and Vector Production – is offering recent graduates and management-level employees the skills to succeed in an industry that will continue to grow and provide good-paying jobs in the future.

CCRM has an exceptionally capable workforce, which we are building through our international networks with academia and industry. Most exciting, we are beginning to seed “CCRM alumni” in companies in the U.S., U.K., Europe and Japan. In fact, in many ways CCRM has been a training ground for industry leaders who launch their careers in our labs.

In Canada and around the world, there are other examples of training programs preparing tomorrow’s CGT leaders, but demand remains high and gaps in expertise are an issue today.

Governments, educational institutes and industry need to come together to ensure that the global CGT industry does not stall and sputter because of a workforce that is too inexperienced to lead, commercialize, manufacture and scale new treatments that will revolutionize medicine. Patients are relying on us!

If talent is an issue that our industry comes together to support, we will all benefit in the long run, along with the patients we are striving to help.

References 1. Regenerative Medicines Market by Therapy (Cell Therapy, Gene Therapy, Immunotherapy, Tissue Engineering), Product (Cell-based, Acellular), Application (Orthopaedic & Musculoskeletal Spine, Dermatology, Cardiovascular, Central Nervous System), Region - Global Forecast to 2021. marketsandmarkets.com. Website, July 2016 2. Alliance for Regenerative Medicine Q2 2018 Data Report 3. KPMG. (2014). Following Through: Realizing the Promise of Stem Cells. Ottawa (ON): Canadian Stem Cell Foundation CCRM is a Canadian leader in developing and commercializing regenerative medicine technologies and cell and gene therapies. It is a centre of excellence funded by the Government of Canada through the Networks of Centres of Excellence program. Michael May is President and CEO of CCRM. Peter Zandstra is the Chief Scientific Officer at CCRM and the Founding Director of UBC’s School of Biomedical Engineering. Zandstra and May co-founded CCRM, which launched in June 2011.

Learn more about CCRM at www.ccrm.ca.

To see this story online visit https://biotechnologyfocus.ca/tacklingthe-talent-gap-in-the-cell-and-gene-therapyindustry/ October/November 2018 BIOTECHNOLOGY FOCUS 15

Alzheimer’s disease

| Donald F. Weaver, MD, PhD, FRCPC

Alzheimer’s

There’s Still Light

at the end of the tunnel

The Problem The spectrum and spectre of Alzheimer’s disease and related dementias are affecting every nation in the world and it’s only going to get worse.

At present more than 45 million people worldwide have Alzheimer’s, a mind-robbing condition that impairs memory, thinking and behaviour, often leading to death within 3 to 9 years after diagnosis.

16 BIOTECHNOLOGY FOCUS October/November 2018

Alzheimer’s disease

Alzheimer’s is not only a profound human tragedy, it also imposes an overwhelming socioeconomic cost in terms of direct medical, social and informal care costs. Due to the length of time people live with the illness and need care, it’s among the most expensive medical conditions in the world and may soon become the costliest disease in human history.

A

dding to this problem, there are 7.7 million new cases per year worldwide – that’s another person with Alzheimer’s every four seconds. The number of people with Alzheimer’s is projected to rise by 55% by 2030, and by 2050 more than 135 million people will be struggling with (and – unless we can find a cure – ultimately dying from) Alzheimer’s. In Canada, some 750,000 Canadians suffer from this, and one new person joins them every five minutes. It is estimated that by 2030, this number will have nearly doubled to 1.4 million. Considering that Alzheimer’s is already the 7th leading cause of death worldwide, the impending toll, as the Alzheimer’s pandemic fully manifests, may become catastrophic.

Alzheimer’s is not only a profound human tragedy, it also imposes an overwhelming socioeconomic cost in terms of direct medical, social and informal care costs. Due to the length of time people live with the illness and need care, it’s among the most expensive medical conditions in the world and may soon become the costliest disease in human history. Dealing with dementia already costs Canadians $15 billion a year, a figure that by some estimates will rise to over $150 billion annually by 2040. In 2015, the total global cost of dementia was estimated to be $818 billion, equivalent to 1.1% of global gross domestic product. It is estimated that if the number of patients increases as projected in the years ahead, the costs to care for them will exceed $1.2 trillion annually in North America alone. Thus, future costs for Alzheimer’s threaten to bankrupt not only individual families but even national healthcare systems. Alzheimer’s and related dementias are a truly immense

problem – a problem that is currently posing potentially insurmountable healthcare and fiscal challenge, and a problem that we cannot afford to ignore any further.

The Disease All Alzheimer’s is dementia, but not all dementia is Alzheimer’s. Dementia is the loss of cognitive functioning – memory, language skills, visual perception, problem solving, self-management, and the ability to focus and pay attention – to such an extent that it interferes with a person’s ability to carry out the day to day activities of their normal life. Dementia is an overall term for a set of symptoms; dementia is not a specific disease. Alzheimer’s, on the other hand, is a specific disease and is a specific type of dementia. Alzheimer’s is an chronic, irreversible, progressive type of dementia that is associated with brain atrophy and with the deposition of abnormal protein clumps, called plaques and tangles, in the brain of the afflicted individual (Figures 1-3). Alzheimer’s is by far the most common type of dementia accounting for approximately 75 per cent of all dementia cases. Other types of dementia include vascular dementia, frontotemporal dementia, progressive supranuclear palsy, Lewy Body dementia, and chronic traumatic encephalopathy. Neither Alzheimer’s nor dementia are a normal part of aging. Alzheimer’s is one of those diseases that is affecting us from “cell to society”, having the ability to harm or even destroy individual lives, families, or possibly even the healthcare system of a country.

October/November 2018 BIOTECHNOLOGY FOCUS 17

Alzheimer’s disease

Atrophic Brain with Alzheimer’s Pathology

The world’s first G8 Dementia Summit was held in London on 11 December 2013, bringing together government ministers, researchers, pharmaceutical companies and charities to discuss what can be done. Delegates agreed that Alzheimer’s is a huge health and economic global challenge with the capacity to threaten the socioeconomic well-being of entire countries; they also heard that these challenges must be met through innovation and that the response to dementia must be a concerted worldwide effort.

At the level of the family, Alzheimer’s can be overwhelming for the families of affected people and for their caregivers. Parents with dementia are often moved into family homes causing domestic stress; typically, children also give up their jobs to care for their dementing parents – causing additional strains within a family unit. At the level of the individual, Alzheimer’s is truly devastating. The disease robs people of their recollections, erases personality and makes even routine tasks like dressing and bathing impossible.

The afflicted individual is unable to recognize their spouse of fifty years and is incapable of identifying their own children. Bigger than cancer, bigger than heart disease or lung disease – for seniors, dementia is the single greatest cause of disability and debilitation.

At the cellular and tissue level, Alzheimer’s is characterized by the death of brain cells (neurons) and the activation of brain support (glial) cells. A normal adult human brain weighs 1300-1400 g; a person who has succumbed to Alzheimer’s will have a brain 18 BIOTECHNOLOGY FOCUS October/November 2018

Normal Adult Human Brain.

Photos courtesy of Dr. S. Darvesh, Halifax

weighing less than 900 g. The thick grey cortical mantle of cells that envelop and embrace the brain (as the cortex) will be especially devastated. Ultimately, plaques (aggregates of beta-amyloid protein) and tangles (aggregates of tau protein) will become the tombstones of dead neurons, as the brain irreversibly degenerates.

At the molecular level, the two protein pathologies characteristic of Alzheimer’s are amyloid plaques composed of Aβ and neurofibrillary tangles of tau. Aβ is composed of 39 to 43 amino acids and is generated by proteolytic cleavage of amyloid precursor protein (APP), a transmembrane protein of unknown physiological function. Cleavage of APP occurs by two competing enzymes: α-secretase and β-secretase. In Alzheimer’s, cleavage by β-secretase at the N-terminus and intramembranous cleavage by γ-secretase at the C-terminus liberates Aβ from neuronal cells. Above a certain critical concentration, Aβ monomers undergo a shape change from a random or α-helical state to β-pleated sheets. This conformational change, known as nucleation, prompts self-assembly into Aβ dimers, trimers and oligomers. Oligomers can further polymerize to form soluble protofibrils, followed by insoluble and highly ordered fibrils that deposit to form amyloid plaques. Small oligomeric clumps of Aβ are toxic to brain and contribute to the cause of Alzheimer’s; the plaques on non-toxic. The other proteopathic hallmark of Alzheimer’s is the presence of neurofibrillary tangles composed of microtubule-associated tau

protein. Normally, tau stabilizes neuronal microtubules in axons, but in Alzheimer’s, abnormal phosphorylation facilitates disassociation from the microtubule and loss of function. Similar to Aβ, the change prompts self-assembly into highly toxic soluble oligomers, which eventually form larger fibrils and tangles that deposit within neurons.

However, (and thankfully) our molecular level understanding of Alzheimer’s is still evolving. In 2018, there are two dominant hypotheses concerning the cause of AD: (1) the proteopathy hypothesis; (2) the immunopathy hypothesis. As discussed above, the proteopathy hypothesis proposes that proteins such as β-amyloid and/or tau misfold and become oligomerized or clumped.

Plaques and Tangles in a Brain with Alzheimer’s Pathology. Photos courtesy of Dr. S. Darvesh, Halifax

Alzheimer’s disease

In Silico Representation of Model Drug Docking to Beta-amyloid Peptide.

Photos courtesy of Dr. A Meek These species become toxic to the brain, destroying neurons and eventually causing Alzheimer’s to progress. The immunopathy hypothesis proposes that immune cells in the brain, called microglia, become “overactive” in Alzheimer’s; these activated microglia elicit the expression of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumour necrosis factor-α (TNF-α) influencing the surrounding brain tissue, damaging neurons and thus causing Alzheimer’s to progress.

The Pessimism In 2018, there are no “disease modifying” or “curative” agents for AD. The only agents on the market for Alzheimer’s are “symptomatic” agents that temporarily help with the symptoms, but do not affect the relentless progression of the disease. Over the past two decades, of the more than 200 compounds assessed as disease modifying agents for Alzheimer’s assessed in more than 400 clinical trials, all have failed – it hasn’t even been close. And these failures have cost the pharmaceutical industry billions of dollars, while understandably diminishing their enthusiasm for continuing in this area. Indeed, a number of large pharmaceutical companies have withdrawn from active research in the dementia field.

The amyloid hypothesis based on blocking the neurotoxic effects of amyloid protein misfolding seemed like such a logical target, yet all drugs exploiting this approach have failed.

This has led to the oft-quoted but probably premature declaration that “the amyloid hypothesis is dead!” Where do we go from here, and do we even have a direction to pursue? Is this a problem that we cannot cure?

The Optimism There is room for optimism – lots of optimism.

An antibody called BAN2401 (a humanized IgG1 version of the mouse monoclonal antibody mAb158, which selectively binds to

large, soluble Aβ protofibrils) when used at its highest dose reduced decline in two measures of cognitive function in Alzheimer’s after 18 months, while reducing amyloid burden, according to data presented by the drug’s manufacture at a conference in July 2018.

While questions persist concerning the study methodology, this is the first large clinical trial to support the proteopathic hypothesis of Alzheimer’s. This is a step in the right direction.

Thus, the design and optimization of a pioneering disease modifying drug must remain as a neuropharmacological priority. The disappointing results of the past 20 years have revealed the pressing need for novel targets in disease-modifying drug design. Currently, four leading hypotheses attempt to explain the etiology of AD: (i) abnormal folding of both Aβ and tau (not just Aβ alone) and their subsequent assembly into oligomers, (ii) neurotoxic activation of the innate immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. All of these hypotheses offer a wealth of druggable targets, offering new avenues of hope. And these are not the only interesting hypotheses.

My own laboratory is contributing to these new avenues of hope (Figure 4). Over the past ten years, we have devised an innovative computer-based (in silico) model of protein misfolding. We identified a common binding site based on epitope commonality between multiple misfolded amyloid proteins. This information was used to create CCM (Common Conformational Morphology), a proprietary methodology for constructing models of the earliest stages of protein misfolding during the initial oligomerization stages – not during the late pre-plaque fibrillization stage. CCM represents a protein shape – not an amino acid sequence – that predisposes proteins to toxic misfolding. Using CCM we performed an in silico screen of 11.8 million compounds, allowing for the identification and optimiza-

tion of numerous classes of potent, drug-like compounds –making structure-based design a reality for anti-amyloid drug discovery.

This has enabled us to pioneer the design of molecular classes capable of preventing the misfolding of Aβ, tau, either individually or together. To develop these agents further, we have founded a biotech company, Treventis Corp. Earlier this year, Treventis announced a strategic research partnership with Servier, an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France. The collaboration covers a large drug discovery program targeting both tau and Aβ and their earliest phases of oligomerization.

As 2018 draws to a close there are many changes giving optimism and hope. The amyloid hypothesis isn’t dead, it has been reshaped and is still a source of druggable targets. New agents will be targeting amyloid misfolding at its earliest stages and will also be tackling the equally important misfolding of tau. Multiple other areas of investigation are still in their infancy but will offer exciting opportunities for drug design. In particular, the role of neuroinflammation and neuroimmunology in the pathogenesis of Alzheimer’s is presenting a bright future for therapeutic opportunities. Everything doesn’t have to be about the neurons; drugs that target the microglial support cells may have the ability to slow disease progression down. There is also a growing realization that there may not be a single magic bullet that takes out Alzheimer’s.

As with high blood pressure, it may take a cocktail of different agents targeting different receptors. All of these realizations are conceptual advances paving the way for the discovery of potentially useful drugs.

Arguably, halting the full impact of the impending Alzheimer’s pandemic may take more than a drug. Alzheimer’s is a disease that devastates not only individuals, but a disorder that afflicts families, societies and nations. And a lot of people already have it and will require care. Addressing this epidemic requires a multi-prong attack, targeting all aspects of this disease, from molecules to cells, from individual lives to their families and societies.

To achieve this goal, we need to better understand all these diverse and varied aspects of Alzheimer’s.

Donald F. Weaver, MD, PhD, FRCPC is Director, Krembil Brain Institute, University Health Network, University of Toronto

To see this story online visit https://biotechnologyfocus.ca/alzheimerstheres-still-light-at-the-end-of-the-tunnel/ October/November 2018 BIOTECHNOLOGY FOCUS 19

Best Practices

| By Michelle Currie

MaRS Innovation continues to tighten the Canadian Innovation-based relationship with South-Korea The world is getting that much smaller as countries expand their reach across the globe, fueling collaboration to stem the gaps in innovation and research.

MaRS Innovation is one of these organisations that are crossing the cultural divide to build a brighter future for tomorrow.

20 BIOTECHNOLOGY FOCUS October/November 2018

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ithin the last few years, MaRS Innovation has built a partnership with the Korea Health Industry Institute (KHIDI) which is a South Korean government-affiliated organization in the healthcare and R&D area which sought to invest in innovative biotech research within North America. After hearing advice that they should investigate the Toronto region and meet with MaRS Innovation, they immediately saw the mutual benefits and began working together for a common cause in June of 2016. Later that year, Raphael (Rafi) Hofstein, the president and CEO of MaRS Innovation flew to Seoul where KHIDI and

MaRS Innovation signed an MOU to begin the journey forward.

Like MaRS Innovation – which is a nonprofit organisation that acts on behalf of their member institutions, including 15 of Toronto’s top universities, institutions and research institutes to bring the most promising research breakthroughs to the global market – KHIDI represents the 10 largest hospitals in South Korea that aim to commercialise the outcome of their research.

The two organisations agreed on three main elements when they signed their MOU in November of 2016: one, to identify complementary scientific projects; two, to determine which scientific technologies would

Best Practices

MaRS Innovation recently returned from Seoul after addressing their second commitment in the MOU, namely incorporation after research for the more promising research breakthroughs.

lend themselves to company creation; and three, to create a fund that will support these fledgling companies once they are up and running.

By that time, they had already identified 10 candidates for the Seoul community of university hospitals, which resulted in remarkable success and led to more operational sessions soon thereafter. The matchup between the Ontarian and South-Korean technologies has been supported by the Ontario and the South-Korean government,

Rafi Hofstein

respectively. Assessments are being held in the two sides of the ocean and the parties strongly believe that funding will continue to be allocated for this promising binational initiative.

“In less than two years it’s become a very dynamic relationship,” says Rafi Hofstein.

“Whenever we go East, we stop there.

Whenever they come West, they stop here.

Needless to say, there are some cultural differences to bridge over, and that really has to be done face to face. What’s beautiful about this relationship is that we made a point of getting together on a regular basis. When they came last year on their North American tour, we announced the second cohort. So far so good as they say, because the two cohorts, the Canadian and the Korean, are actively pursuing science and complement each other’s expertise.”

Additionally, they invited Dr. Christopher Yip from the University of Toronto (UofT) who oversees international partnerships and is associate vice president of UofT. Thus far, Yip has sought after partnerships with India and China, but after being introduced to the two largest university hospitals in Korea, he sees this as a promising opportunity for binational partnership.

This collaboration has provided the companies with the funds they need for their joint activities and has had such an overwhelmingly positive response that MaRS Innovation has started visualising the third cohort, which Rafi thinks will reflect the growing trend of artificial intelligence, machine learning and big data processing in health care.

MaRS Innovation recently returned from Seoul after addressing their second commitment in the MOU, namely incorporation after research for the more promising research breakthroughs. With MaRS Innovation’s exceptional portfolio of over 50 companies,

10 in the first and second cohort, they have identified at least three projects that will undoubtedly turn into companies soon. It will be a joint venture between the two groups.

They are in various leading areas of healthcare namely, drug development, molecular diagnostics and drug delivery. The next step of the journey will be the most challenging part of the MOU – a bumpy but crucial part of the path – and that is access to capital.

MaRS Innovation met in recent months with several financial groups from the two sides of the ocean, and discussion are underway relative to jointly support the nascent companies.

“We wanted to have the freedom to invest in Korea and in Canada,” says Rafi. “We had to be very selective in terms of who was eligible to make investments outside South Korea, and I think we did a good job on that.

But much more intriguing is the non-government financial players who stood out to be promising ventures that may move to the next level and facilitate further discussions.

Rafi adds, “I can not hide my excitement.

I find the Koreans to be the right people in terms of willingness to do business with us here in Canada. I’m very pleased with everything we have accomplished so far, and I truly believe that it’s just the beginning of something that is going to be very fruitful and productive.”

“Moreover”, suggested Rafi “in the wake of Samsung opening their AI Centre in the MaRS Discovery District, Toronto will undoubtedly be gaining more international momentum as eyes across the world see this bustling city as a destination for innovation.

To see this story online visit https://biotechnologyfocus.ca/marsinnovation-continues-to-tighten-the -canadian-innovation-based-relationshipwith-south-korea/

October/November 2018 BIOTECHNOLOGY FOCUS 21

| By Steven Lynum

How to Evaluate Your Next Ultra-Low Temperature Freezer Purchase: Caveat Emptor

The development of ultra-low temperature freezers spans decades of progress in component design, electronic supervision and cabinet construction.

22 BIOTECHNOLOGY FOCUS October/November 2018

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rom refrigerants and compressors to controllers, cabinet insulation and data logging, manufacturers have established a myriad of internal operating metrics shaped to position their ultra-low temperature freezers as the best on the market.

In recent years, however, the industrywide creation of ENERGY STAR® criteria for universal assessment of freezer performance has begun to bring credible, third-party insight into a reality that was previously left to manufacturers alone.

Today, facility and biorepository managers, along with end users, are becoming more knowledgeable about key performance factors that ultimately define the suitability of an

PERSPECTIVE

The exponential worldwide growth in the volume of stored frozen biologicals has brought forth a demand for better energy management.

ultra-low temperature freezer for their application. As a result, the demand for independent testing and comparative evaluation of leading ultra-low temperature freezers on the market has grown, while purchasers have broadened their view of freezer specifications to evaluate the concept of performance at a higher level.

This embraces three primary deliverables essential to stored product safety: reliability, recovery and energy efficiency. The first of these is reliability.

Reliability Because an ultra-low temperature freezer is acquired to safeguard years or even decades of clinical research at temperature setpoints of -80°C, or -70°C, failure is never an option.

The value of frozen contents is difficult or even impossible to determine. Specimens are often irreplaceable. Therefore, uptime is the most important function of an ultra-low temperature freezer. It is also the single most challenging attribute that leads to uncertainty and impact on reproducibility in scientific research.

This chronic uncertainty weighs on the entire industry. The global repository of generations of research depends on the performance of a cold storage product group that, if not properly engineered, places inordinate stress on the machines as well as the people who place their life’s work inside.

In the life science market, there is no central agency to corroborate manufacturers’ claims of reliability, uptime and other performance attributes critical to safe storage of biological materials. Purchasers must depend on the integrity and social responsibility of the manufacturer, truthfulness of published specifications, referrals from colleagues and testing performed by their own institutions or by independent agencies.

Consultation with facility maintenance personnel responsible for out-of-warranty service, or those who are factory trained and authorized to perform in-warranty service, can be highly credible sources of information.

Independent service repair companies with reputable service technicians are unlikely to recommend poor performing freezers in order to earn money fixing them; the stakes are too high. Whether in-house or independent companies, these insights can offer valuable context in advance of a purchase decision.

Recovery The exponential worldwide growth in the volume of stored frozen biologicals has brought forth a demand for better energy management. New cooling systems have established impressive statistics for reducing power requirements. These include cascade platforms with variable speed compressors as

well as alternative engines. All must maintain ultra-low temperatures for indefinite storage while restoring setpoint temperature quickly and efficiently following door openings.

Unfortunately, the need to reduce energy consumption has pushed some systems to the edges of prudent performance.

Temperature recovery requires a combination of system anticipation and rapid platform response within the parameters of a safe mechanical performance envelope.

Thus, the freezer must be designed for the worst-case reality of daily operation where room temperatures can be high, line voltages may fluctuate due to aggregate power demands leading to brown-out conditions, and access to stored product may be more frequent than normal. The accumulation of frost on door gaskets and dust on condenser coils is another reality that engineers must confront.

While recovery and uniformity are related, recovery speed, which is a prime indicator of reserve refrigeration capacity and high ambient temperature tolerance, remains at the forefront of performance attributes. Interior temperature recovery and uniformity are essential to the relationship between storage location and the viability of stored product over the long term.

A thorough evaluation of ultra-low temperature freezer purchase alternatives demands an understanding of recovery rates, measuring criteria such as ambient temperature at time of test, control probe location, duration of outer and inner door openings, and freezer load. Manufacturers who publish best-case recovery rates measured under ideal conditions may not account for actual use scenarios in their literature.

Independent documentation of recovery performance should be a prerequisite when comparing competitive freezers, and an essential consideration when purchasing any ultra-low temperature freezer whether for replacement or new laboratory design.

October/November 2018 BIOTECHNOLOGY FOCUS 23

PERSPECTIVE

An energy-efficient freezer that cannot respond to high ambient temperatures or cannot recover quickly following door openings neglects a key requirement for stable, long-term storage at ultra-low temperatures.

freezers should be made only within the context of why freezers are required in the first place: reliable, uniform and responsive ultra-low temperature storage of critical research.

Toward this end, purchasers should demand comparative data generated through independent evaluation of all products under consideration. Through this effort, test conditions and criteria should remain constant across the board so that strengths and shortcomings can emerge in support of a purchase decision.

Summary While manufacturers’ specifications typically offer features and benefits, dimensions, site preparation and voltage requirements, the operation of an ultra-low temperature freezer in situ is best evaluated by a systematic review of third-party or internally commissioned testing independent from manufacturers’ claims.

An example of an internally commissioned comparison of ultra-low temperature freezers was presented at the International Society for Biological and Environmental Repositories (ISBER) 2018 Annual Meeting, Dallas, TX, “Comparison of Energy Efficient -80°C Freezers for Biorepository Storage.”

Here, the Mayo Clinic Biorepository Program Biospecimens Accessioning and Processing (BAP) Core Laboratory compared three leading upright ultra-low temperature freezers under controlled conditions.

Energy Efficiency Development of more energy efficient ultralow temperature freezers has continued to reveal significant improvements in the interplay between electronic sensors embedded within the cooling circuit, firmware with algorithms programmed to anticipate cooling demand, and cooling engines or compressors designed to remove heat from the cabinet to the outside environment. As a result, the power consumption gap between leading ultra-low temperature freezers from various manufacturers has narrowed. Today, purchasers must emphasize reliability over initial acquisition cost. Purchasers must demand temperature recovery and uniformity more than insignificantly different energy costs. And purchasers must demand a rebalanced performance equation where reliability, recovery and operating costs are properly 24 BIOTECHNOLOGY FOCUS October/November 2018

apportioned to protect a priceless inventory.

An energy-efficient freezer that cannot respond to high ambient temperatures or cannot recover quickly following door openings neglects a key requirement for stable, long-term storage at ultra-low temperatures. The industry-wide adoption of ENERGY STAR criteria for measuring and documenting power consumption has offered a new set of standards by which freezers can be evaluated. Energy consumption alone, however, should not be a primary performance attribute if achieved at the expense of recovery and uniformity.

As energy efficiencies continue to equalize, customers should expect energy savings over the life of the freezer that supersede the cost of operating installed freezers running on older conventional platforms. Most importantly, investments in energy efficient

This report is available from The Mayo Clinic or at https://www.morressier. com/article/5ada8a0ed462b8029 238e4de?utm_source=laboratoryfocus&utm_medium=editorial&utm_ campaign=ult-freezers.

Steven Lynum is President, PHC Corporation of North America, formerly known as Panasonic Healthcare Corporation of North America, a subsidiary of PHC Holdings Corporation, Tokyo, Japan, which is a global healthcare company involved in the three core businesses of Medical Devices, Healthcare IT and Life Sciences.

To see this story online visit https://biotechnologyfocus.ca/how-toevaluate-your-next-ultra-low-temperature-freezer-purchase/

Across Canada

| By Michelle Currie

Riding the biotech current to PEI:

Q&A

with Rory Francis, PEI BioAlliance

Canada has a lot to offer, especially in the biotech space. But certain regions dominate in some categories more than others. Prince Edward Island is no exception.

It may be a small island lying just off the coast of Nova Scotia and New Brunswick, but when it comes to bio-based human, animal, and fish health technologies, the province punches above its weight.

Biotechnology Focus had the pleasure to speak with the executive director of the PEI BioAlliance, Rory Francis, who discussed in detail how the innovation ecosystem is mapped out in the province to give an informative view on what makes up this powerful dynamic. As an experienced senior executive with over 30 years experience in professional, management, and leadership roles in the private and public sectors, Rory Francis has helped lead transformative change in several programs and services across the province of Prince Edward Island.

October/November 2018 BIOTECHNOLOGY FOCUS 25

Across Canada

Q: Before delving into what is going on in the current innovation ecosystem on Prince Edward Island, could you give us a little bit of background on the PEI BioAlliance and the vision of the organization?

The BioAlliance has been around for almost 14 years now. It was created in 2005 as a private-not-for-profit organization led by the private sector leaders in the community here in Prince Edward Island (PEI). But the DNA of the organization is such that our board includes those private sector leaders, as well as academic and research partners – university, college, National Research Council, Agriculture Canada Research – as well as government partners in federal and provincial agencies, and several organizations involved in finance. So, it really is a cluster model very much like a Michael Porter model partnership among various stakeholders all committed to developing and executing on a single strategy to develop the bioscience cluster in this province. That really hasn’t changed over the last decade in terms of its role. It’s really a private sector led economic

development engine focused on the biotech sector in the province.

Q: Have you been with the BioAlliance

since inception?

Yes, I have been here since inception. I was asked to help put some structure into what a small group of companies was, but there really was no structure or strategy at that time. That’s what I was asked to assist with.

So, it’s really all kinds of leaders from all those partners that came together to think through what our model should be, what the role of the BioAlliance should be within the community, and in particular, what mattered in terms of creating an environment for business. And when I say ‘role’, that’s very important because there are various kinds of clusters in the world and economic development models. So how are we defining success? What does that look like? It is a very important conversation to have early on in any organization. What’s essential is being clear on what success looks like and then setting up some stretch goals and strategies to get there.

26 BIOTECHNOLOGY FOCUS October/November 2018

Q: What is the scale of the cluster?

We are about 57-58 companies here in Prince Edward Island in the bio sector, with over 1600 employees, $250-million in sales per year, about $80-million in R&D investments each year, and we also track one of our key metrics - follow on capital.

One of our roles is really helping early-stage companies, both those that are born here in the province and early-stage companies from other jurisdictions and countries see the value in being within the cluster here to help them commercialise their technology. That is a very important goal we set out early on; to be good at establishing the conditions for those earlystage, technology-rich, maybe business plan poor companies to increase the probability of them actually getting to the market successfully. That really means focusing on what matters in terms of making that transition and being able to get through that critical path from the technology to a real business. Follow on capital is an important metric because that’s an indication of whether or not we’re actually getting companies to a point where they are attracting private sector investment.

Across canada

The BioAlliance Inc. is a relatively small organisation - the catalyst for the development of the strategy that the board owns and then facilitating the execution of that strategy through our partnership – which is an absolutely key part of what differentiates us and how we work.

Q: Now, what is the ratio of the companies within the cluster? Do they tend to be heavier on the early-stage side or do you have more mature companies in the region?

Of the 58 companies I mentioned earlier, about half of those would be about prerevenue. So, they are working through their clinical program. They’re working through their regulatory requirements in order to take a technology to market, but they’re not in the market yet. The other half would be companies that actually have products in the market. That’s a pretty healthy ratio for the bio sector in general.

The other metric that is kind of interesting is that about half the companies within our cluster are born and bred here; the other half are from somewhere else in the world and have chosen to locate here in our backyard as part of the cluster. They feel that it’s strategically important for them to be here versus anywhere else in the world to commercialise their technology. So, that’s a pretty big vote of confidence in the cluster environment, the ecosystem here and what we have established.

Our largest companies are still small by international standards, with $50-100-million a year revenue and up to 300 employees.

These include companies like BioVectra, Sekisui, and Elanco. We also have a second tier of companies that have approximately 100 employees at the $20-million mark, all the way down to the really early-stage companies, with one or two scientists trying to commercialize their technology and get the proof of concept work done.

Q: What is the draw then for these companies to relocate to PEI if they were not originally from your backyard?

It’s not so much about moving. We’re not talking about moving companies that already exist in some other jurisdiction in Canada or even in the US and setting up shop in Prince Edward Island, unless it is with a view of accessing Canadian markets or North American markets. In terms of the companies, they are usually early-stage companies. We focus on due diligence, the technology assessment, a hard-nose screening of what kind of opportunities these companies have for success as part of an incubation program that we run.

The strategic reason for being here is usually the technology support - the science and technology underpinning and areas of strength have a lot to do with what companies are here and why. Areas that are being reborn in terms of new development are natural health products, personal health care products, even pharmaceuticals, animal health, animal nutrition. So natural health products – these are extracts from marine and terrestrial sources of bioactives – and that whole area of expertise is something that we really do have here and are probably one of the leaders in the country in that area.

Animal Health and Nutrition is another focus area, with expertise within both the private and public sectors. We have the Atlantic Veterinary College (one of five in North America) located here in Prince Edward Island. Fish health and nutrition is another niche area, and a very fast-growing market in the world (aquaculture). We really own the leading assets in North America when it comes to fish health and nutrition, everything from again businesses who have very strong expertise in vaccine research and development, commercialisation, manufacturing, contract research capacity, that supports the stringent regulatory requirements of putting these products into the marketplace and infrastructure that can support that R&D. So, we have a really sophisticated platform October/November 2018 BIOTECHNOLOGY FOCUS 27

Across Canada

well-integrated support for companies One of our roles is of working in fish health and nutrition. really helping earlyQ: Going back to the PEI BioAlliance, stage companies, both what is your operating model? those that are born here The BioAlliance Inc. is a relatively small - the catalyst for the developin the province and organisation ment of the strategy that the board owns early-stage companies and then facilitating the execution of that strategy through our partnership – which is from other jurisdictions an absolutely key part of what differentiates and how we work. It’s this partnership and countries see the us that we’ve established over quite a few years value in being within now that involves the business community, the academic and research community, and the cluster here to help our government partners that allows us all to row together and focus on the same set of them commercialise priorities. You can get a lot of things done in of overall strategy and how we work their technology. terms with individual companies when we have everyone understanding what matters and working together to find solutions at a cluster level and at the business level.

Collaboration is a word that gets a little kicked around, but I think we’ve got a lot of years now of evidence that if you can establish that kind of an attitude if everyone (whether we’re talking private sector or academia or government agencies) sees that their mandate is more quickly and more readily fulfilled by being part of something bigger than themselves, then everyone is willing to commit resources and time to make things happen.

Q: What would you say is the defining success of the organization?

28 BIOTECHNOLOGY FOCUS October/November 2018

If we go back to our metrics, we have been pretty aggressive on setting targets for cluster growth. The last full turn of the strategy wheel from 2012-2015, we were able to double private sector revenue, increase job numbers by 50 per cent, and increase access to capital dramatically.

Some other highlights over the last few years would be that we’ve been very competitive, and very successful in national competitions. We established the Emergence Bioscience Business Incubator through success in a national competition and have been running that incubator program as a virtual incubator for almost five years. We have 65 companies that are additional companies outside of what I talked about earlier.

About 20 of those are from Prince Edward Island, but the other 45 are from other parts of Canada, the U.S., Europe, Australia, and Israel. It is a very successful incubator program that is not only assisting bio companies across Canada in getting their technologies to market, but we are serving a soft landing program for companies from other countries who are, for example, from Europe, who want access to the North American marketplace and they have a technology that fits with our strengths here in Prince Edward Island. So, our incubator program has been a highlight and I think a very strong element of the cluster ecosystem here.

Natural Products Canada was born here in 2016 winning a national competition, CECR (Centre for Commercialization and Research) program, which was a very big deal. It’s a $25-million over 5-year program.

Natural Products Canada now has offices in five provinces and is really an accelerator, supporting companies in the natural product space with equity investment, with connections to other sources of capital. They’re helping companies that are a little beyond the incubator side of things. In fact, we’ve had companies come out of our incubator program and receive capital investment from Natural Products Canada, taking them to the next level. It’s been a very exciting new initiative with its own board, its own structure.

But it is really creating a national network of expertise in the natural product space.

We’re also part of the Ocean Supercluster, representing the marine bio resources component. There’s a lot going on and many exciting opportunities ahead.

To see this story online visit https://biotechnologyfocus.ca/riding-thebiotech-current-to-pei-q&a-with-rory-francis-pei-bioalliance/

Biotechnology Focus delivers critical Canadian news and insights, trends and reports, from R&D to business.

www.biotechnologyfocus.ca Focused on moving innovation forward

Special Report

| By Laurence MacPHIE and Donald Bocchinfuso Bereskin & Parr LLP

Patent Protection for Stem Cells Expanding Opportunities

T

herapeutic applications of stem cells are central to the promise of regenerative medicine. An increasing number of stem cell therapies are being approved for clinical use and by some estimates the global market is expected to grow to ~5 billion dollars by 2024. However, commercializing any therapeutic application is difficult. Careful consideration of patent strategy at the outset of R&D is critical for establishing a competitive advantage.

Different jurisdictions have different restrictions on what may be patented.

In most cases, claims directed to isolated stem cells as well as therapeutic uses of those cells are permissible in Canada and Europe as long as the

30 BIOTECHNOLOGY FOCUS October/November 2018

claims meet the remaining criteria for patentability such as novelty and inventiveness. In the United States, isolated products of nature are no longer considered patentable subject matter. This may limit the availability of patent protection for cells that are not “significantly different” from those found in nature. Nevertheless, it is often possible to obtain effective protection by adopting different claim strategies. For example, in the U.S. one strategy is to pursue product claims to any commercially relevant combinations of stem cells and other elements (such as a scaffold or agent that results in the combination having characteristics that are markedly different from those found in nature),

while pursuing relatively broad method claims that refer to the cells per se for the treatment of a medical condition. Claims to recombinant stem cells should be considered patentable subject matter in the U.S., Canada and Europe.

Cell-based therapeutics will often have complexities in their manufacture not seen with small molecules.

Claims directed towards advances in the analysis, preparation or storage of stem cells can have significant commercial value. Remember to expand your IP diligence beyond immediate therapeutic applications and work with a patent agent to consider whether additional opportunities exist for patent protection.

CALENDAR October 2018

November 14-15, 2018

Email: euro@pharmaceuticalconferences.org Phone: 1-213-233-9462 1-888-843-8169

13th World Congress on Pharmacology and Toxicology 2nd International Conference on Cancer Biology Melbourne, Australia and Drug Delivery Email: pharmatoxicology@ new card_Layout 1 2/9/2018 11:25 AM Page 1 Los Angeles, US pharmaceuticalconferences.org Phone: 1-888-843-8169 Phone: 1-213-233-9462 Email: cancerbiology@oncologyseries.com 1-888-843-8169 Web: https://cancerbiology.conferenceseries.

November 15-16, 2018 com/ 9th Global Experts Meeting on October 18-19 2018 Neuropharmacology 13th World Pharma Congress Berlin, Germany Warsaw, Poland Phone: 1-888-843-8169 Email: pharmacongress@ pharmaceuticalconferences.org Web: http://world.pharmaceuticalconferences. com/

October 3-4 2018

October 24-25 2018 5th International Conference on Stress Disease and Medicine Boston, US Phone: 1-888-843-8169 Email: oxidativestress@conferencesamerica.org Web: http://stress.pharmaceuticalconferences. com/

October 24-25, 2018 13th International Conference on Biopharma and Biotherapeutics Boston, Massachusetts, USA Phone: 1-213-233-9462 1-888-843-8169 Email: biopharma@annualamericacongress.org

October 24-25, 2018 13th International Conference on Biologics and Biosimilars Boston, USA Phone: 1-888-843-8169 Email: chrisofc06@gmail.com biosimilars@annualamericacongress.com

November 2018 November 5-7 2018 18th Annual Pharma Middle East Congress Abu Dhabi, UAE Phone: 1-800-216-6499 Email: pharmaceuticalcongress@ pharmaceuticalconferences.org

November 15-16, 2018 14th International Conference on Generic Drugs and Biosimilars Berlin, Germany Email: genericpharma@ pharmaceuticalconferences.org Phone: 1-213-233-9462 1-888-843-8169

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