Biotechnology Focus December 2012/January 2013

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

DECEMBER 2012/JANUARY 2013 VOLUME 15, NUMBER 11

EPIGENOMICS Providing new tools in the war on cancer

INSIDE:

The flow of capital in public and private markets in Canadian Life Sciences

CO2 Solutions

capturing innovation

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16 Developing an innovative and sustainable solution for carbon capture

contents December 2012/ January 2013 – VOLUME 15 – NUMBER 11

11

11 Epigenomics, providing new

Epigenomics and cancer research

tools in the war on cancer

Opinion

with NA ing ons.

oval tors, are cing

gy to and elds

Dr. Martin Hirst discusses epigenomics and how it can provide a new understanding of how cancer works (By Shawn Lawrence)

18 Commercializing Regenerative Medicine The effort to commercialize regenerative medicine in Canada is growing steadily. In the emerging field of regenerative medicine, slow and steady wins the race (By Stacey Johnson)

mple nes: film, more.

cess:

FEATURES

25 Opinion

Fostering Great Leadership (By Nathalie Richard)

DEPARTMENTS

IN EVERY ISSUE

16 Innovator 6

Research news

9

Business corner

When developing an innovative and sustainable solution for carbon capture, CO2 Solutions took its inspiration from a powerful muse: Mother Nature (By Daniela Fisher)

26 new products

21 Across Canada

28 Calendar of events

8

al to sage

R&D News

New research centre key to renewing biopharmaceutical research in Québec

www.biotechnologyfocus.ca

A look at public and private markets for Canada’s life sciences industry in the third quarter of 2012 (By Jacki Jenuth)

29 The Last Word

Improving investor confidence amidst clinical failures (By Robert Foldes)

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 3

PUBLISHER’S NOTE

PUBLISHER/ EDITOR-IN-CHIEF STAFF WRITERS

Terri Pavelic Shawn Lawrence Daniela Fisher

CONTRIBUTING WRITERS

The future of medicine: going beyond healthcare On November 15, MaRS Discovery District held its fourth annual Future of Medicine Conference. This year’s event focused on market challenges for medical technology companies, and how we can transform the healthcare system. The conference featured insightful presentations and panels from industry experts on market trends, access to capital and FDA requirements for medical devices and technology.

At the event, presenters highlighted the issues facing the healthcare industry, including an aging population riddled with chronic diseases and the need to reform healthcare goals. The conference also addressed the difficulty in securing capital for biomedical innovation and getting hospitals, and the healthcare system at large, to adopt new technologies and systems.

With over 180 delegates in attendance, the event started off with a keynote lecture from renowned cardiologist Dr. Theodore Schreiber, president of the Cardiovascular Institute, Vanguard Health Systems, speaking on how innovation in cardiovascular medicine is changing our world and the landscape of medicine.

He talked about the process issues in healthcare, touching on unavoidable medical realities such as the fact that we are an aging population, with everyone living longer in part because of innovations in medicine and treatment. However, with the current model for treating patients, Dr. Schreiber cautioned, the goal is saving patients not curing them. While we are developing more effective treatment methods, we are not curing the chronic diseases, thus increasing co-morbidities in patients.

Dr. Schreiber also looked at past and present innovations in cardiovascular surgery, and the need for preventative measures and healthier living, focusing on overall wellness instead of life expectancy.

Following Dr. Schreiber was a presentation by Hamid Sadri, director of Health Economics and HTA at Medtronic. He spoke about the changing dynamics of point of care delivery and recent med tech innovations that allow for remote care and monitoring of patients. Sadri discussed the emerging field of telemedicine, and how new technologies are allowing healthcare providers to access and analyze physiological, imaging and diagnostic data through secure Internet-based platforms.

The day also featured presentations from Nitin Kaushal, managing director in deals practice at PricewaterhouseCoopers (PWC), on market trends for medical technologies, and from Katherine Bonter, director of promotion and advocacy at Cepmed, who spoke about perspectives on the industry’s regulatory environment.

It concluded with pitch presentations from up-and-comers in the medical device and healthcare information technology sectors.

In conclusion, the conference highlighted the fact that we are at a crossroads in the evolution of healthcare. As industry, government and academia work to transform our healthcare system and its goals, the future is bright for innovation in the med tech sector.

To see more coverage of this event, visit our new website at www.biotechnologyfocus.ca. Happy Holidays!

Jacki Jenuth Robert Foldes Stacey Johnson Nathalie Richard

NATIONAL ACCOUNT MANAGER GRAPHIC DESIGNER CONTROLLER MARKETING MANAGER CIRCULATION DIRECTOR

Marcello Sukhdeo Elena Pankova John R. Jones Mary Malofy James Watson circulation@promotive.net Tel: 705-812-0611

EDITORIAL ADVISORY BOARD celine Bak, Analytica Advisors; Rob henderson, BioTalent Canada; najla guthrie, KGK Synergize; pierre Bourassa, IRAP, Montréal; murray mclaughlin, Sustainable Chemistry Alliance; carol Reynolds, Wordmark Consulting Group Inc.; ulli Krull, UTM; John Kelly, Erie Innovation and Commercialization; Peter Pekos, Dalton Pharma Services; Brad thompson, Oncolytics; Darrell ethell, CanReg; John hylton, John H. Hylton & Associates; Robert foldes, Cognovie Inc.; Randal R.goodfellow, P.Ag., Senior Vice President, Corporate Relations, Ensyn; Bob h. sotiriadis, Robic LLP; dale patterson, Genome Canada; Darcy Pawlik, Syngenta Seeds Canada Inc; Gail Garland, OBIO; Barry gee, CDRD; Bonnie Kuehl, Scientific Insights Consulting Group Inc.; Raphael hofstein, MaRS Innovation Biotechnology Focus is published 10 times per year by Promotive Communications Inc. 24-4 Vata Court, Aurora, Ontario L4G 4B6 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 dept – 24-4 Vata Court, Aurora, Ontario L4G 4B6 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.

If you would like to order hard copy or electronic reprints of articles, contact Sandra Service 905-727-3875 x221 reprints@promotive.net ABC Membership Applied For.

4 BIOTECHNOLOGY FOCUS December 2012/ January 2013

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R & D NEWS Merck invests in Montréal’s life sciences research sector

From left to right: Dr. Jean-Claude Tardif, Director, MHI Research Institute, Dr. Jacques Turgeon, Director, CHUM Research Centre, Mr. Cyril Schiever, President and Managing Director, Merck Canada, Dr. Vassilios Papadopoulos, Executive Director, RI-MUHC and Mr. Martin LeBlanc, Vice-Chairman of the Board, Montréal InVivo. (CNW Group/MERCK) Merck Canada announces it will invest $12.5 million to fund research at three university-affiliated and hospital-based research centres.

The three centres that will receive funding are: • the Research Institute of the McGill University Health Centre (RI-MUHC); • the CHUM Research Centre (CRCHUM); • and the Montréal Heart Institute Research Centre (MHI).

“Merck is dedicated to supporting Québec’s life sciences community, and we are proud to work in collaboration with the industry, government and academia,” said Cyril Schiever, president and managing director, Merck Canada. “We believe initiatives like investing in top research institutes that conduct innovative basic and translational research are one of the best ways to improve R&D productivity and stimulate innovation in Québec.”

“Montreal is a leader in the life sciences research sector in North America thanks to the presence of world-class research institutions such as those who will benefit from this announcement,” added Martin Leblanc, vice-chairman of the board,

Montréal InVivo. “Partners like Merck Canada help ensure that future discoveries by local scientists will keep impacting the lives of patients not only in Québec, but around the world.”

The funding brings the total Merck investments to date in the province to approximately $60 million. In March, Merck announced a $35 million investment in the Merck Lumira Biosciences Fund, as its primary investor and only pharmaceutical industry partner. The fund, established by Merck in collaboration with Lumira Capital, Teralys Capital and other partners, provides investment capital to support early stage life science innovation in Québec.

Prior to that Merck invested $6.8 million in AmorChem, a Québec life sciences venture capital fund, to increase the commercial potential of quality academic research carried out in Québec, and $5 million in the Québec Consortium for Drug Discovery (CQDM), which funds projects for the development of innovative tools and technologies that accelerate the drug discovery process.

To see this story online visit http://biotechnologyfocus.ca/?p=2874

IRCM researchers discover nerve cell’s internal clock A group of researchers at the Institut de recherches cliniques de Montréal (IRCM) have discovered the internal clock of a nerve cell, used during embryonic development. The study, led by Dr. Frédéric Charron, was published in the scientific

journal Neuron. The discovery of the internal clock was made in collaboration with Dr. Alyson Fournier’s laboratory at the Montreal Neurological Institute.

6 BIOTECHNOLOGY FOCUS December 2012/January 2013

continued on page 7

Clinical Trials & Patents n Bioniche Life Sciences Inc. (Belleville, ON) has discontinued its Phase 3 clinical trial with Urocidin™ in non-muscle-invasive bladder cancer. The trial, a randomized, active-controlled, open-label, multi-centre study with a blinded endpoint assessment designed to compare Urocidin™ with mitomycin C in the intravesical treatment of patients with BCG recurrent or refractory nonmuscle-invasive bladder cancer, was being run by the company’s global licensing partner, Endo Pharmaceuticals, a subsidiary of Endo Health Solutions. The trial has not been recruiting at the expected rate and, after recent discussions with the U.S. Food and Drug Administration (FDA) regarding the current clinical trial design, Endo has decided to end the study before its scheduled completion.

Endo and Bioniche are jointly considering potential next steps for the program. n Allon Therapeutics Inc. (Vancouver, BC) announces that patient treatment has been completed in the multinational pivotal Phase 2/3 clinical trial that is evaluating the company’s lead product davunetide as a potential treatment for progressive supranuclear palsy (PSP), a rapidly progressing and fatal degenerative brain disease. Allon expects to disclose top line data from this pivotal study in the second half of December. n Bayer Inc. (Toronto, ON) and the Population Health Research Institute (PHRI), a joint Institute of Hamilton Health Sciences Corporation and McMaster University, have initiated the COMPASS trial, the largest clinical study of the oral anticoagulant rivaroxaban to-date. COMPASS is a Phase 3 trial that will investigate the prevention of major adverse cardiac events (MACE) including cardiovascular death, myocardial infarction and stroke in patients with coronary artery disease (CAD) or peripheral artery disease (PAD).

The COMPASS study will assess the potential of rivaroxaban to provide additional prevention of cardiovascular events to patients when added to an antiplatelet therapy, as well as investigating rivaroxaban and an antiplatelet as single treatments. The study will be conducted in collaboration with the PHRI and will enroll approximately 20,000 patients from more than 450 sites across more than 25 countries. In Canada, the study will enroll approximately 2,250 patients from more than 45 sites and will represent a significant investment in Canadian-led research over the next several years.

For more R&D news visit http://biotechnologyfocus.ca/?cat=71

Continued from page 6 Their findings could lead to the development of new tools for repairing and regenerating nerve cells following injuries to the central nervous system.

At Dr. Charron’s laboratory, researchers study neurons, looking at how the neurons navigate through a developing embryo to arrive at their correct destination.

“To properly form neural circuits, developing axons (long extensions of neurons that form nerves) follow external signals to reach the right targets,” says Dr. Frédéric Charron, director of the Molecular Biology of Neural Development Research Unit at the IRCM, in a release. “We discovered that nerve cells also have an internal clock, which changes their response to external signals as they develop over time.”

In the study, IRCM scientists examined the Sonic Hedgehog (Shh) protein, which gives cells important information for the embryo to develop correctly. The Shh protein also plays a key role in the central nervous system’s development.

“It is known that axons follow the Shh signal during their development,” says Dr. Patricia Yam, research associate in Dr. Charron’s laboratory and first author of the study. “However, axons change their behaviour once they reach this protein, and this has been a mystery for the scientific com-

munity. We found that a nerve cell’s internal clock switches its response to external signals when it reaches the Shh protein, at which time it becomes repelled by the Shh signal rather than following it.”

“Our findings therefore showed that more than one system is involved in directing axon pathfinding during development,” says Dr. Yam. “Not only do nerve cells respond to external signals, but they also have an internal control system. This discovery is important because it offers new possibilities for developing techniques to regenerate and repair damaged nerve cells.

Along with trying to modify external factors, we can now also consider modifying elements inside a cell in order to change its behaviour.”

Every year, injuries to the central nervous system affect thousands of Canadians and can lead to lifelong disabilities. Most often caused by an accident, stroke or disease, these injuries are very difficult to repair.

New tools are therefore required to repair damage to the central nervous system, including techniques that could potentially regenerate nerve cells.

“The Canadian Institutes of Health Research is delighted to support research aimed at improving the lives of individuals with damage to the brain or spinal cord,” says Dr. Anthony Phillips, scientific director

Dr. Frédéric Charron

R & D NEWS

of CIHR’s Institute of Neurosciences, Mental Health and Addiction. ‘’Nerve cell repair and regeneration remains an important health challenge, and we believe that Dr. Charron’s research findings will contribute to the solution.”

The research project was funded by grants from the Canadian Institutes of Health Research (CIHR), the Peter Lougheed Medical Research Foundation, the McGill Program in NeuroEngineering and the Fonds de recherche de Québec – Santé (FRQS).

To see this story online visit http://biotechnologyfocus.ca/?p=2748

RDC announces $1.6 million in R&D funding to 18 Newfoundland and Labrador companies The Research & Development Corporation of Newfoundland and Labrador (RDC) has announced investment support that will assist several provincial companies with research and development (R&D) projects in Newfoundland and Labrador’s priority sectors such as natural resources, ocean technology, aquaculture, advanced manufacturing and information communications technology. In all 18 business-led projects will receive more than $1.6 million in funding from the RDC. “Newfoundland and Labrador’s support for R&D is assisting these businesses to conduct leading-edge research that’s attracting international attention,” said Research & Development Corporation Minister Keith Hutchings. “These companies are directly contributing to our economy,

RDC announced more than $1.6 million for 18 Newfoundland and Labrador-based companies doing innovative R&D including Blue Oceans Satellite Systems of St. John’s. Paul Anderson, the company’s president and CEO, spoke during the announcement. (CNW Group/Research & Development Corporation)

creating jobs and wealth, and further establishing Newfoundland and Labrador as a leader in R&D and innovation.”

“By making strategic investments in R&D projects and capabilities, the Research & Development Corporation is helping businesses pursue new ideas, innovative technologies and opportunities that enhance Newfoundland and Labrador’s competitive advantage,” added Glenn Janes, CEO of RDC. “Supporting business-led R&D is a priority area for RDC investment.”

The funding comes from two RDC programs designed to improve business-led R&D in Newfoundland and Labrador.

Both RDC programs provide funding to support companies as they increase their R&D expenditures and develop leadingedge technologies. Programs details are available online at www.rdc.org.

To see this story online visit http://biotechnologyfocus.ca/?p=2705

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 7

R & D NEWS New research centre key to renewing biopharmaceutical research in Québec AstraZeneca Canada and Pfizer Canada, two leaders in the country’s biopharmaceutical industry, are forming a partnership with the Québec government to create the NĒOMED Institute, a new kind of life sciences research centre. A total of $100 million will be invested to establish and support the research centre over the next five years.

The NĒOMED Institute will act as a catalyst in two ways: first, by creating a bridge between academic research and life sciences companies; second, by providing an environment that will create synergies between the main biotech industry players. The non-profit research hub will seek to bring together stakeholders in the research and development chain. More than 100 highly qualified employees are expected to be working there when it reaches full capacity.

According to the partners, the launch of the new biopharma research centre is a reflection of the changing face of R&D in the biopharmaceutical industry. The Institute will bring pharma and biotech companies,

venture capitalists, and contract research organizations (CROs) all under the same roof for drug development and research.

It will be located in a former AstraZeneca building in Technoparc Montréal.

“The cost of discovering new drugs keeps rising and pharmaceutical companies need to adapt,” said Max Fehlmann, the new president and CEO of the Neomed Institute.

“The Neomed Institute, acting as a competitive actor in the drug development sector, will allow Québec’s scientists to make the bridge between academic innovations and commercial opportunities in a better way.”

AstraZeneca Canada is donating $35 million to the Institute. The investment includes land, the neuroscience basic research facility, and leading-edge laboratory equipment. It also includes the donation of intellectual property to three AstraZeneca pain molecules and projects, as well as $5 million to support the activities of the Institute.

Pfizer Canada is providing a financial contribution of approximately $3.5 million, and the Québec government is contributing $28 million towards the project.

“We are excited by Neomed because it

Photo: Max Fehlmann, CEO of the NĒOMED Institute, in a Nov. 23 press conference.

Photo courtesy: Jessika Duquette www.jessikaduquette.com. exemplifies the type of partnership activity that is needed in our new R&D model,” said John Helou, president of Pfizer Canada Inc. “Neomed complements our long-time Canadian R&D investment strategy which has been focused on innovative partnerships.”

To see this story online visit http://biotechnologyfocus.ca/?p=2863

OICR and MaRS Innovation to fund development of nanotechnology-based cancer drug

Drs. Mark Ernsting (left) and Shyh-Dar Li, inventors of Cellax™ at the Ontario Institute for Cancer Research (OICR) The Ontario Institute for Cancer Research (OICR) and MaRS Innovation announce that OICR will provide $1.5 million in funding over the next three years to further develop Cellax™, a nanoparticle drug that could offer an alternative to chemotherapy with fewer side effects.

“Cellax is promising because it provides a more targeted strategy for treating tumours, killing tumour cells while minimizing the effect on healthy tissue,” said Dr. Rima Alawar, director, OICR’s Medicinal Chemistry Platform. “OICR is proud to invest in a technology that has such potential to one day improve quality of life for cancer patients.”

Cellax, invented by Dr. Shyh-Dar Li and his research team in OICR’s Medicinal Chem-

exploit this weakness. We hope to use the NanoCMC platform to deliver drugs that will build up only in tumours. This would spare patients the side effects associated with less targeted treatments, which damage healthy cells as well as tumours.”

OICR is supporting the Cellax project through its Intellectual Property Development and Commercialization (IPDC) Fund, which was established to bridge the gap in the commercialization process between public funding agencies and private investors. All IPDC candidate projects are rigorously reviewed by external subject-specific experts in business and technology.

“MaRS Innovation provided the Cellax project with early-stage funding along with business development and management through our high-touch, embedded model,” said Dr. Raphael Hofstein, president and CEO of MaRS Innovation. “MI continues to lead Cellax’s commercialization strategy. We believe Cellax meets a clear clinical need within the multibillion-dollar Taxane market, and we anticipate that Cellax will emerge as a significant new player.”

istry Platform group, is a drug-polymer conjugate based on Dr. Li’s proprietary NanoCMC™ technology. These polymers self-assemble into defined nanoparticles and, when injected, selectively accumulate in tumours. Because of this property, the drug is released where it is most needed, increasing therapeutic benefits and reducing the side effects associated with conventional chemotherapy.

With the new funding, the Cellax team will conduct the pre-clinical manufacturing and toxicology studies necessary to bring Cellax to a clinical trial in cancer patients.

“Tumours are by nature more permeable to nano-sized molecules than normal tis- To see this story online visit sue,” says Li. “We are developing Cellax to http://biotechnologyfocus.ca/?p=2580

8 BIOTECHNOLOGY FOCUS December 2012/ January 2013

BUSINESS CORNER Prince Edward Island’s biotech companies will have new support for getting their businesses from the R&D stage to the market. The province’s new Commercialization Services Initiative (CSI) offers companies advice on how to speed up the commercialization process.

The Initiative is supported by the Atlantic Canada Opportunities Agency, the National Research Council of Canada Industrial Research Assistance Program (NRC-IRAP) and Innovation PEI. Through CSI, companies have access to expertise in all areas of the commercialization process where that expertise does not reside within the company. This includes areas such as: intellectual property management, market assessment, regulatory strategy, finance, business strategy, and technology assessment.

“Even great technologies can fail to achieve market success if the commercialization plan isn’t well-developed and well-executed. This initiative will help our small and medium-sized companies access external know-how that will improve their results,” says Rory Francis, executive director of PEI BioAlliance. “The BioAlliance and its government partners foresee an

Rory Francis

Revving up PEI’s bio businesses

increase in company revenues and jobs, and reduced risk to the public and private investments that are often backing early stage companies.”

Francis says that Canada’s underperformance in successfully commercializing new products and technologies had been a matter of great concern for many years.

Dr. Debbie Plouffe who directs the Centre for Aquaculture Technologies Canada in Fortune Bridge, PEI, says her company is in

the early stages of establishing a contract research service for fish health and aquaculture companies around the world.

“The CSI has allowed us to carry out a global market assessment to identify clients and competitors, and really determine our competitive advantage working from here in PEI,” said Plouffe.

To see this story online visit http://biotechnologyfocus.ca/?p=2899

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 9

BUSINESS CORNER

The Centre of Excellence for the Prevention of Organ Failure (PROOF Centre) and HTG Molecular Diagnostics have finalized a license agreement that gives HTG Molecular Diagnostics exclusive rights to market a PROOF Centre-developed blood test for COPD prognosis.

The gene expression blood test will be used for the prognosis of COPD patients who could experience frequent exacerbations, or “lung attacks.” HTG Molecular Diagnostics will develop the test on its qNPA platform. The PROOF Centre will be involved in the clinical validation in Canada, and provide leader support for regulatory approval in North America.

Lung attacks are the leading cause of emergency room visits and hospitalizations among chronic disease sufferers, accounting for over $5.7 billion direct, and $6.7 billion indirect healthcare costs every year in Canada alone.

“The development of these blood tests has been driven by a huge unmet clinical and social need,” says Dr. Bruce McManus, director of the PROOF Centre. “This agreement with HTG Molecular Diagnostics will facilitate bringing these tests to market faster, provid-

Bruce McManus looking at a sample with trainees

PROOF Centre and HTG Molecular Diagnostics commercialize COPD prognostic test

ing physicians with tools to improve patient care and management and help alleviate suffering of patients with COPD.” At present, physicians have limited capabilities to predict which COPD patients will suffer frequent lung attacks. Identifying these patients earlier allows physicians to intervene sooner and personalize treatment for each patient to prevent future attacks.

“Delivery of an accurate, early predictor of frequent patient lung attacks, and pro-

viding the ability to personalize preventive care is of paramount importance to pulmonology practitioners and patients,” says TJ Johnson, CEO of HTG Molecular Diagnostics. “This agreement is the first of many that HTG Molecular Diagnostics and PROOF Centre hope to have to bring medically valuable biomarker tests to the clinic.”

To see this story online visit http://biotechnologyfocus.ca/?p=2197

Dealmakers n CML HealthCare Inc. (Mississauga, ON) has signed an exclusive licensing agreement with early disease detection company Mitomics Inc. (Thunder Bay, ON) to make its Prostate Core Mitomic Test™ (PCMT) available in Canada.

Under the agreement, Canadian urologists will be able to order the PCMT through CML HealthCare in early 2013. Specimens will be analyzed at Mitomics’ CLIA laboratory in Aurora, CO. n KLOX Technologies Inc. (Laval, QC) has entered into an agreement for the sale of its professional in-dentists-office whitening kit business as well as its teeth-whitening pen business to Valeant Pharmaceuticals International, Inc. (Montréal, QC) which will be managed by its dental affiliate OraPharma, Inc.. Valeant plans to launch the products in the U.S. in early 2013. Financial terms include an upfront payment and a double-digit royalty stream based on product sales during the next 10 years.

Lignol Energy Corporation (Burnaby, BC), a company in the advanced biofuels and ren

newable chemicals sector, has completed the purchase of an additional 88,000,000 ordinary shares of Australian Renewable Fuels Limited for an aggregate purchase price of $1.1 million.

This pruchase increases the company’s investment in Australia’s largest biodiesel producer from 11.2 per cent to 14.9 per cent. n Tekmira Pharmaceuticals Corporation (Burnaby, BC), a developer of RNA interference (RNAi) therapeutics, has obtained a worldwide, non-exclusive license to a RNAi technology called Unlocked Nucleobase Analog (UNA) from Marina Biotech, Inc. (Bothell, WA) for the development of RNAi therapeutics. Under the license agreement, Marina will receive an upfront payment plus milestone and royalty payments on products developed by Tekmira that use UNA technology. Financial terms of the license agreement were not disclosed. n Stem Cell Therapeutics Corp. (Toronto, ON) has signed an agreement with University Health Network (Toronto, ON) through its

10 BIOTECHNOLOGY FOCUS December 2012/ January 2013

commercialization agent MaRS Innovation (Toronto, ON). The agreement provides Stem Cell Therapeutics with an option to an exclusive worldwide license to an innovative cancer stem cell program. Based on Dr. Aaron Schimmer’s award-winning research, the technology has provided compelling evidence that tigecycline, an FDA-approved antibiotic, is able to selectively target leukemia cells and leukemic stem cells by shutting down their energy supply through the inhibition of mitochondrial protein synthesis. SCT has been granted an option by UHN under which prior to April 30, 2013, SCT may conclude the exclusive license provided SCT has secured additional financing sufficient to support its product development operations.

The worldwide, exclusive license agreement will contain customary provisions regarding an initial license consideration, milestones, royalties on sales and sublicensing terms.

For more Business Corner news visit http://biotechnologyfocus.ca/?cat=78

By Shawn Lawrence

Bruce McManus looking at a sample with trainees

CANCER RESEARCH

epigenOmics PROVIDING NEW TOOLS IN THE WAR ON CANCER Image: Martin Krzywinski

O

ne of the biggest breakthroughs so far in the war on cancer was the realization that it is essentially a genetic disease. However, as we learn more about cancer, it becomes clearer that what’s written in our DNA is only part of the story; there are other factors at work that go beyond genetics.

It is on this latter point that a new area of research, known as epigenetics, is building upon our knowledge of the genetics of cancer. Epigenomics, defined broadly, is the study on how the genome responds to the environment and how this response can have a long-term impact on the activity of our genes. To understand what epigenomics is one must first start with the definition of the term “genome”: the entire DNA content of a cell. In contrast, the term “epigenome” refers to chemical modifications of the DNA itself and of proteins that control the structure and activity of the genome.

The genome remains mostly the same throughout an individual’s life, whereas the epigenome changes dramatically – but in very precisely controlled ways – during normal development and aging. Deviations from these normal changes in the epigenome can have profound effects on which genes are turned on and hence can cause cells to behave abnormally. More specifi-

project management staff to develop and operate a world class epigenome mapping pipeline founded on the Illumina massively parallel sequencing platform over the last six years. The centre operates several genome-scale cores, including a biospecimen core; a sequencing core; a library core; an engineering core; a cally, they can cause the onset of cancer.

Canada’s Michael Smith Genome Sci- technology development core; a quality asences Centre (GSC),a department of the surance core; an informatics core; and a sysBC Cancer Agency (BCCA) in Vancouver, tems core. Each core has a group lead, and is staffed by skilled and experienced Canada, is very active in exploring technical and scientific staff who how to use epigenomics as a work together to operate tool against cancer. In early critical infrastructure, as 2012, the GSC launched genes can nOt Only well as plan and execute the CEEHRC (“Canadian be inactiVateD by genetic experiments.

Epigenetics, EnvironAs the head of epigment and Health RemutatiOns, but alsO by Dna enomics at the GSC, search Consortium”) methylatiOn, which in the Dr. Martin Hirst is epigenomics platform currently involved in and data coordination case Of a tumOr suppressOr several cancer-specific centre, funded by the gene, can cOntribute tO epigenetic projects.

Canadian Institutes of the DeVelOpment “I’ve always been inHealth Research and terested in transcriptional Genome BC. Of cancer. regulation, the study of how Since its early days in 1999 genes are turned on and off,” the GSC, under the leadership of Dr. Hirst explains. His entry into the field Dr. Marco Marra, has steadily grown and now occupies 50,000 sq. ft. and currently of epigenomics in 2006 coincided with employs approximately 310 staff members. the introduction of a revolutionary DNA In addition to its core services the GSC has sequencing technology, massively parallel created a team of scientific, technical and sequencing.

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 11

CANCER RESEARCH

According to Dr. Hirst, before the arrival ied, this mark is dramatically reduced in of these devices, there really was no way of the malignant cell population. In addition, doing large scale or whole genome epigen- imbedded within this genome-wide loss of DNA methylation there are specific regions, etic studies.

“The DNA sequencing platform was then called CpG islands, that become hypercalled the Solexa 1G Sequencer (since ac- methylated, and can affect the control of quired by Illumina Inc.), and it held great nearby genes. For example, there are cases promise because it enabled the sequenc- of tumour suppressors that are genetically mutated, so they become inactive. In the ing of millions of short DNA fragments context of breast cancer that would simultaneously. At the time of be BRCA1. BRCA1 can also be its introduction, the platform inactivated through DNA was capable of generatmethylation, so this epiing 10s of millions of One of the key genetic modification that short DNA sequences limitations with current occurs actually shuts the - ideally suited for the gene down and results sequencing of epigepigenomic sequencing in the loss of the tumour enomic libraries – in technologies, is the suppressor protein. Just a sense it gave birth as a genetic mutation of to the field of epigsubstantial requirements the gene would inactivate enomics.” of tissue or cells. the gene because it’s nonCurrently, there are 11 functional, it can be shut off Illumina HiSeq 2000 platthrough epigenetic mechanisms forms, two Illumina HiSeq as well. And there is also a sort of 2500s, three Illumina miSeqs and collusion where it seems that in certain one Ion Torrent Personal Genome Machine performing sequencing at the GSC. Sequenc- cases, one of the gene copies (called alleles) ing capabilities include both single-end (50 can be genetically inactivated and the other and 75 base read lengths) and paired-end allele, becomes methylated and thereby sequencing (50, 75 and 100 base read turned off. So it really does seem as though lengths). The GSC has to date constructed the genetic and epigenetic phenomena over 25,000 libraries and generated over are really intertwined. And finally in many 267 terabases (2.67 x 1014) of data on the Il- cancers, in particular in hematopoietic malumina sequencing platform, contributing to lignancies or blood cancers, what’s come numerous national and international projects out in the last three or four years of deep genome sequencing, is that many of them and high impact publications.

Using this technology, Dr. Hirst and his contain genetic mutations in the genes collaborators are piecing together how tran- which encode for proteins that regulate the sient and stable chemical modifications to epigenome.”

The goal is to understand how these our DNA and associated proteins (known collectively as our epigenome) cause our enzymes behave, how they affect the degenome to stay healthy or develop diseases. velopment of cancer, with an ultimate goal Initially, the researchers are investigating of applying these findings to develop new changes to tissues and cells that lead to can- diagnostics and therapeutics. Specifically, cers such as leukemia, as well as cancers of if an enzyme adds or removes too many the colon and ovaries, all of which are the modifications, and thereby causes cancer, you can try to inhibit that enzyme. most common human malignancies.

One remarkable finding that has come “Going back now almost three decades, researchers have been examining epigenetic about from this field of research, says Dr. phenomena in the development and pro- Hirst, is that epigenome changes are reversgression of cancer, and we now know that ible. Several inhibitors of chromatin-modifycancer can be defined by both genetic and ing enzymes, including histone deacetylase and DNA methyltransferase inhibitors, have epigenetic disruptions,” says Dr. Hirst He explains that what this means is that demonstrated clinical anti-cancer activity. these genetic and epigenetic alterations Dr. Hirst explains that this new understandare intimately linked to one another. One ing of how cancers work has the potential example he gives is a chemical modification to yield new treatments.

“There are clinical trials using epigenof DNA called methylation.

“In nearly all cancers that have been stud- etic based therapeutics, for example, DNA 12 BIOTECHNOLOGY FOCUS December 2012/ January 2013

methylation inhibitors are being used in the clinic to treat certain types of leukemia, and the thought is that by inhibiting DNA methylation, you can release that repressive signal that’s present on tumour suppressor genes, allowing those genes to then be transcribed and then those genes can tell the cell things have gone wrong.”

The GSC-BCCA team has had its own success story around one such enzyme: EZH2.

The GSC-BCCA team discovered a mutation in this gene, which had not been previously associated with cancer, in certain kinds of lymphoma. These findings were published in 2010 in the international journal Nature Genetics.

“It was a key finding and one that emphasizes the highly collaborative work that defines the GSC. The initial finding would not have been possible without a close collaboration with clinical colleagues at the BC Cancer Agency, Drs. Gascoyne and Connors, who provided primary cancer tissue for molecular profiling. Building on this discovery are groups led by Dr. Humphries at the Terry Fox Laboratory, developing mouse models to study the functional consequences of the mutation and Dr. Aparicio working on inhibiting the mutant enzyme.”

Not surprisingly, working with clinicians is a critical component of what scientists at the GSC do.

“Clinicians are our partners and collaborators, who provide invaluable expertise and access to primary human tumour samples.

Without these critical connections we would not be able to perform these epigenetic studies. These collaborations are an essential component of translational research, helping to drive emerging technologies into the clinic.”

The discovery of the role of EZH2 has directly led to companies pursuing an inhibitor to EZH2, with the hope of having some efficacy in the treatment of certain types of lymphoma.

In addition to its work understanding enzymes, the GSC is also developing new applications for massively parallel sequencers.

“The technique that I started with in terms of my entry into epigenomics for example, is a technique called ChIP (Chromatin Immunoprecipitation) sequencing. That was not a technique that the company had even considered for that application – they were focussed on genome sequencing.”

Continued on page 14

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CANCER RESEARCH Continued from page 12

Photo by Chuck Russell

“I think it’s a very exciting time to be part of this field because we are at the dawn of being able to read the epigenome and this will lead to greater understanding of how the epigenome contributes to normal and diseased states.” — Dr. Martin Hirst Another application that Dr. Hirst and the GSC team helped develop was RNA sequencing. His team has created new protocols for what is called mRNA-seq. It turned out to be an important tool for studying the role of EZH2 mutations.

In addition to his work with the GSC, Dr. Hirst also operates out of his lab, the Laboratory of Epigenomics and Chromatin Biology at the Centre for High-Throughput Biology at the University of British Columbia. The work conducted at UBC focuses on developing technologies to make the sequencing of the epigenome more efficient. One of the key limitations with current sequencing technologies is that when sequencing an epigenome, significant amounts of material like tissues or cells are needed. Dr. Hirst’s goal is to reduce the amount of input material so that researchers will be able to analyze the genome or the epigenome from small numbers of cells with the ultimate go of profiling single cells.

“This entails developing new assays and working with other basic scientists at UBC, and then transferring these methodologies to the GSC, which is taking those developed protocols and applying them to a production environment in the context of primary human material.”

Dr. Hirst is also part of a number of initiatives with goals to deliver a complete reference of epigenome information on a full spectrum of normal and malignant mammalian cell types; develop novel molecular and computations technologies for broader application of epigenomic research in the future; and characterize the impact of epigenetic modifier mutations emerging from international cancer genome sequencing efforts. This includes generating highresolution reference epigenome maps that can be exploited to provide new insights into many diseases and finding new means to control them.

In Canada, the GSC is one of the two Canadian epigenome mapping and data centres under the umbrella of the Canadian Epigenetics, Environment and Health

Research Consortium. In addition, the GSC also contributes, as the only foreign member institution, to the NIH Reference Epigenome Consortium.

“We work with Dr. Costello from the University of California, San Francisco (UCSF) who leads one of the four roadmap centres. We provide epigenetic mapping expertise to that project. We have been working on this project for four years and have generated reference epigenomes for various brain, breast, blood, skin, embryonic and

Image: Martin Krzywinski

14 BIOTECHNOLOGY FOCUS December 2012/ January 2013

now working on placenta cell types.”

“Large scale human reference epigenome mapping which was initiated by the NIH reference epigenome mapping consortium, has

CANCER RESEARCH now been partnered with initiatives in Canada, (CEEHRC), a European project called Blueprint (a large-scale European research project that includes 41 leading European universities, research institutes and industry entrepreneurs) as well as projects in Germany, Italy, South Korea and Japan who are working together as part of the International Human Epigenome Consortium to generate 1,000 human reference epigenomes over the next five years.”

With his expertise in epigenomic mapping, Dr. Hirst is chairing the International Human Epigenome Consortium Assay Standards working group.

“You can think of this in the same way as one would think of the reference human genome project, which has revolutionized human medicine. What we are attempting to do is define references for the many cell types that are present in the body, to provide baseline data for the study of variations that occur normally in the human population and alterations that occurs as a consequence of disease.”

Unlike the reference human genome, where the genome is for the most part the same throughout the body, the epigenome is actually cell type specific. As such, the context of the International Human Epigenomic Consortium is to provide replicated references for approximately 200 human cell types.

“That is why we need 1,000 reference epigenomes and not just one as was the case for the genome. We will need to capture the breadth of different cell types present in the human body. Where will it go from there, I would imagine the next phase will involve understanding variation present in the human population.

One exciting and largely unexplored area is how environmental signals are patterned in the epigenome. Model organism and epidemiological studies have shown that environmental cues such as stress, maternal care, nutrients, toxins etc. seem to be patterned through the epigenome. And these patterns can be inherited. It is as if the epigenome is providing shorterterm plasticity to respond to environmental changes much as the genome does on much longer time scales.

That’s one of the many exciting aspects of epigenetic research in general.”

Dr. Hirst is excited by the promise of what might arise from these collaborations.

“I think it’s a very exciting time to be part of this field because we are at the dawn of being able to read the epigenome and this will lead to greater understanding of how the epigenome contributes to normal and diseased states.”

And as was the case with the EZH2 enzyme, he foresees that future discoveries in epigenomics will aid in the war on cancer.

To see this story online visit http://biotechnologyfocus.ca/?p=2203

Success A CELEBRATION OF

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www.lifesciencesontario.ca December 2012/ January 2013 BIOTECHNOLOGY FOCUS 15

By Daniela Fisher

innovAToR

CO2

SOLUTIONS When it comes to developing innovative and sustainable solutions, nature can be a powerful muse.

capturing innovation

When it comes to developing innovative and sustainable solutions, nature can be a powerful muse. Such was the case for the Québec City-based company CO2 Solutions.

Operation of an enzymatic lab-scale triphasic reactor at CO2 Solutions’ lab

A

n innovator in its field, the clean tech company is using an enzyme found in humans, as well as in all other living things, for carbon capture.

This enzyme, carbonic anhydrase, is a potent biocatalyst and nature’s way of efficiently managing carbon dioxide by converting it to bicarbonate. In the human body, that process happens in the blood and lungs. Inspired by this natural process, CO2 Solutions developed and commercialized this enzyme for use in a patented ‘industrial lung’ that allows for the efficient capture of carbon dioxide produced by power plants and other large stationary emitters.

Its biomimetic technology uses carbonic anhydrase in an energy-efficient solvent to scrub the carbon dioxide from industrial flue gases, such as those produced by coal-fired power plants or aluminum refineries. Once the CO2 has been separated, it can be used in other industrial processes or sequestered underground. The use of carbonic anhydrase as a biocatalyst in the process greatly reduces the capital and operational costs

normally associated with carbon capture.

Through this innovative process, CO2 Solutions has succeeded in offering industry a more efficient tool for managing carbon dioxide emissions.

At the helm of the company is Glenn Kelly, its president and CEO. He sees CO2 Solutions as an emerging part of the energy industry.

“I think we’re going to be adding a new stage to the energy industry, which is the management of the emissions industry produces,” says Kelly. “For me, the innovation we offer represents a logical step forward in what I believe is going to be a big part of the energy industry’s future.”

A veteran of the oil and gas industry, with a civil engineering background, Kelly joined the company as a board member in 2008 and became CEO later that year. Right from the beginning, Kelly’s interest was piqued by the company’s innovative technology and he has used his wealth of industry knowledge to guide the firm’s progress.

“I just saw that this was a great technol-

ogy, it was a tiger in a cage and I thought it had tremendous potential,” says Kelly.

“Carbonic anhydrase is the best catalyst or accelerator yet to be discovered for the management of CO2 conversion into other products. We’ve taken a process from nature and adapted it for large-scale carbon capture.”

The company’s breakthrough technology grew out of work done at Laval University in the late 1990s, when researchers first began to study the use of carbonic anhydrase for carbon capture. The success of that research eventually led to the founding of CO2 Solutions in 1997.

Sylvie Fradette worked on the initial research project while completing her PhD in chemical engineering at Laval University.

One of the original developers of the technology, today Fradette is the company’s vicepresident of R&D. She looks back on how the company first developed its carbon capture technology, after validating that the enzyme could be used to remove carbon dioxide from flue gas.

“The complete idea was to make a system

“I think we’re going to be adding a new stage to the energy industry, which is the management of the emissions industry produces. For me, the innovation we offer represents a logical step forward in what I believe is going to be a big part of the energy industry’s future.”

— Glenn Kelly

16 BIOTECHNOLOGY FOCUS December 2012/ January 2013

innovAToR

Immobilization work in CO2 Solutions’ lab where we could capture CO2, as carbonic anhydrase does in our blood. Our lungs transform that captured CO2, which is in bicarbonate form, back into the gas which we exhale,” says Fradette. “In our technology, the captured carbon dioxide is either used for other industrial applications or sequestered underground.”

Developing the proprietary technology was not a simple process, in large part because the cost of carbonic anhydrase was exceptionally high.

“In the first stages of the company, in the early 2000s, carbonic anhydrase cost $250,000 a gram, which was quite expensive,” says Kelly. “We brought that cost down to about $500 a gram, and even less now, to a couple hundred dollars a gram, because we’re producing it at much larger scale.”

In the early days, the company’s researchers worked on developing their own enzyme. Starting first with human carbonic anhydrase, they synthesized the enzyme in the lab, immobilized it, and then modified it to make the enzyme more robust.

“At the beginning, when we looked at if we could purchase the enzyme, cost was a real issue,” says Fradette. “So it became important in developing this technology to immobilize or keep the enzyme captive in the system for reuse. The objective of this work was to attach the enzyme to supports located in the low temperature, absorptions part of the scrubbing process, and by doing this we were able to keep the enzyme out of the high temperature regeneration part of the process and thus make the lifetime of the enzyme longer.”

Once the researchers had successfully produced and immobilized the synthetic carbonic anhydrase, cost came down and larger scale testing began. From 2003 to 2005, the company ran proof-of-concept testing at the Alcoa aluminum smelter, in Québec, as well as at the Québec City waste incinerator.

“In both cases we were able to show that the enzyme was working quite well. It was successful in capturing CO2 on a significant scale at both facilities,” says Kelly.

After establishing the enzyme’s large-scale

potential for carbon capture, the next major milestone for the company was in 2009, when CO2 Solutions signed a development agreement with Codexis Inc., a Silicon Valley company that enhances naturally occurring enzymes.

“They worked with us to produce some super enzymes that survive at much higher temperatures and in much harsher conditions than anything we’ll find in nature,” says Kelly. “We were also able to do away with the support system and blend this more robust enzyme directly into the solvent.”

The cost for producing this improved enzyme, says Kelly, is in the range of $10 to $100 per kilogram—a striking drop from the initial cost of $250,000 per gram.

With the stronger, cheaper enzyme from Codexis, the company would go on to further collaborate with aluminum producer Alcoa Inc. in 2011, to capture carbon dioxide emissions from aluminum production, and to neutralize some of Alcoa’s industrial wastes using the CO2 byproduct.

CO2 Solutions also improved its technology, making the entire process more efficient. In its new platform (Figure 1, p. 24), flue gas flows into the absorber column on the left. This column contains the solvent infused with the super enzyme. The flue gas rises up the column, bubbling through the solvent which scrubs it of CO2. The super enzyme works like soap does in water, accelerating the purification process and increasing carbon capture by 50 to 70 times.

The carbon dioxide-free gas then leaves at the top of the column.

Meanwhile, the CO2 rich solvent flows through a filtration system, which captures the enzyme and channels it back into the absorber column for reuse. The solvent then flows on into the second column, the stripper column, where it is heated to extract the carbon dioxide from the liquid. The pure CO2 is channeled out the top of the second column for compression and storage or for reuse.

“The big costs that industry faces relative to CO2 capture are the capital costs of hardware and, more importantly, the operational costs associated with the energy required to boil off the pure CO2,” says Kelly. “Without COntInued On page 24

“The objective of this work was to attach the enzyme to supports located in the low temperature, absorptions part of the scrubbing process, and by doing this we were able to keep the enzyme out of the high temperature regeneration part of the process and thus make the lifetime of the enzyme longer.

— Sylvie Fradette

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 17

REgEnERATivE MEdicinE

EFFORTS TO COMMERCIALIZE

ReGeneRatiVe MediCine

IN CANADA GROWING STEADILY By: Stacey Johnson

D

Dr. John B. Gurdon

Dr. Shinya Yamanaka

Stem cells have been around for half a century yet therapeutic progress has been slow.

October 8, 2012 was a great day for the global stem cell community when Drs. John B. Gurdon (University of Cambridge) and Shinya Yamanaka (Kyoto University) were awarded the Nobel Prize in Physiology or Medicine for their work in discovering “that mature, specialized cells can be reprogrammed to become immature cells capable of developing into all tissues of the body.”

This was some serious vindication for a field that has had its share of detractors.

The reasons for that are many, including the huge financial investment in a field that has yet to reach its promised potential.

With a lot of activity lately, that could be changing and the Nobel Prize appears to recognize that fact. Dr. Gurdon’s awardwinning nuclear transfer work took place in 1962. In contrast, Dr. Yamanaka’s successful research to reprogram cells to pluripotency

(the ability to differentiate into fetal or adult cells) was only six years ago. Since then, his lab experiments have progressed into a potential therapeutic to restore sight (the Japan times online Oct. 12, 2012 “Riken to test iPS cells in human trial”).

Commercialization in Canada So where are we, in Canada, in terms of commercializing stem cell and biomaterialsbased products and therapies (i.e. regenerative medicine)?

As far as company creation is concerned, a “MaRS Regenerative Medicine Report” from 2009 identified 11 Canadian companies in this space and today that number is probably closer to 15.1 Here are some findings from Industry Canada’s “Canadian Asset Map for Stem Cell and Regenerative Medicine” (March 2011):

• The federal government is funding two national organizations that focus on commercializing stem cells and/or Regenerative Medicine (RM): the Stem Cell Network, established in 2001, was awarded $63.62 million between 2001 and 2012 to enable the translation of stem cell research into clinical applications, commercial products or public policy. The Network has spun off or grown 12 new or young Canadian companies on the basis of its funded research, research that has led to 120 patent applications and 37 issued patents in the last three years alone; the Centre for Commercialization of Regenerative Medicine, launched in June 2011, was established to accelerate the commercialization of RM technologies COntInued On page 20

18 BIOTECHNOLOGY FOCUS December 2012/ January 2013

Read it here first.

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

Don’t get left behind.

www.biotechnologyfocus.ca

REgEnERATivE MEdicinE “By matching clusters of academic research expertise with the business community, we expect CCRM to play a major role in helping the emerging regenerative medicine field reach its full commercial potential.”

— Suzanne Fortier

COntInued frOm page 18 by bringing together business leadership and innovative stem cell and biomaterial technology development. It will receive $15 million between 2011 and 2015; • At least 39 Canadian researchers were identified as moving scientific findings from the lab to the clinic, but the actual number is expected to be higher; • The Stem Cell Network says its approximately 100 researchers have spent around $50 million on basic and translational research since 2001; • In 2000, clinicians at the University of Alberta published “the Edmonton Protocol” in the new england Journal of medicine demonstrating the first proof of principle that Type 1 Diabetes could be treated effectively using replacement beta cells; • Other protocols are underway for multiple sclerosis, graft-versushost disease, stroke, pulmonary hypertension, neuroblastoma and other diseases that can be treated with stem cells.

When the Industry Canada report was being developed, the Centre for Commercialization of Regenerative Medicine (CCRM) was just getting established. With a mandate that focuses solely on the development of foundational technologies to commercialize stem cell- and biomaterials-based discoveries, the regenerative medicine community is watching CCRM with great interest and anticipation.

“By matching clusters of academic research expertise with the business community, we expect CCRM to play a major role in helping the emerging regenerative medicine field reach its full commercial potential,”

says Suzanne Fortier, chair of the Networks of Centres of Excellence (the federal body that funds CCRM). “The centre’s work keeps Canada at the leading edge of the world’s efforts to turn research breakthroughs into effective therapies.”

In its first 18 months, CCRM has established formal partnerships with Canada’s academic and business communities and formed global collaborations to help strengthen the translation of regenerative medicine around the world.

“The Canadian and international RM community has been very receptive to CCRM, allowing us to accomplish a great deal in a short amount of time,” says Dr. Peter Zan-

the ‘go to’ place for global RM investment and to make Canadian discoveries available to patients to improve their lives.”

As scientific progress takes time, so too does the investment that goes into turning discoveries into safe, viable products for the market. Despite the immense pressure to succeed and expectations from media and the public that stem cells are the “holy grail” of medicine, strong regulatory enforcement is designed to prevent premature product adoption until safety and efficacy have been confirmed.

We all know that the turtle beat the hare in Aesop’s fable. Here too, slow and steady will win the race.

“We’re proud of the strong industry linkages that we’ve made and firmly believe that relationships with academia and industry will facilitate bridging the commercialization gap.”

— Dr. Peter Zandstra

dstra, CSO of CCRM. “We’re proud of the strong industry linkages that we’ve made and firmly believe that relationships with academia and industry will facilitate bridging the commercialization gap.”

A close working relationship with MaRS Innovation, another federally funded centre for commercialization of research, adds additional commercialization clout to the community. MaRS Innovation commercializes the life sciences in Canada and shares its considerable expertise and experience with CCRM. Adds Dr. Michael May, CEO of CCRM: “We won’t commercialize everything, nor will it happen immediately. But we’ve made strategic partnerships and hired the right people to see RM commercialization flourish in Canada. CCRM is driven to make Canada

20 BIOTECHNOLOGY FOCUS December 2012/ January 2013

References 1. The Centre for Commercialization of Regenerative Medicine has partnered with several RM companies not included in the 2009 MaRS report.

Stacey Johnson is the Communications Manager with the Centre for Commercialization of Regenerative Medicine (CCRM). CCRM is developing a Canadian asset map in regenerative medicine that will be available for distribution in 2013. Please e-mail Stacey.johnson@ccrm.ca to be put on the list to receive a copy.

To see this story online visit http://biotechnologyfocus. ca/?p=3041

By Jacki Jenuth

Across Canada FEATURE

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Canadian Life Sciences and the flow of capital

a look at public and private markets in the third quarter of 2012 In Q3 2012, Canadian life sciences companies raised $70.6 million from public and private markets, which was much lower than the $263.3 million raised in the same period last year. Of that total, $56.7 million was invested by VCs over six deals.

Leading the pack was Lumira Capital’s investment in Thrasos Therapeutics, which closed a $35 million round. Proceeds from this round will be used to develop the company’s product, THR-184, which has the potential to reduce the incidence of acute kidney injury in patients undergoing surgeries for coronary artery and valvular disease.This deal is the largest financing of a venture-backed life sciences company in Canada this year and is among the top four deals across all sectors (only one larger financing has closed this year). The round included several corporate investors including SROne, the corporate VC arm of GlaxoSmithKline, who led the round; GSK Canada Life Sciences Innovation Canada Fund; and MP Healthcare Venture Management, the venture arm of Mitsubishi Tanabe Pharma. Merck Lumira Biosciences Fund, ATV Ventures, Pappas Ventures and Fonds de solidarité FTQ also joined the deal along with previous backer SW Co. Newcomer DeNovaMed, a Halifax-based developer of novel anti-

bacterial drugs, was seeded to the tune of $500,000 by Nova Scotia investment firm Innovacorp, and also received a loan from ACOA for $500,000. The company is developing small molecules using computer models, and ultimately hopes to target superbugs like MRSA. Saskatchewan-based Phenomenome Discoveries raised $3.6 million to continue discovery and development efforts related to novel metabolite biomarkers. The investment was made by the Golden Opportunities Fund, a labour-sponsored investment fund based in the province with an economic development mandate.

In silico drug design firm Zymeworks added to its recent successes by closing on an $11 million financing led by the Advanced Biotechnologies Venture Fund group of funds and included Prestige Corporation, Holland Park Global Investment Fund, The Vincent Wildlife Trust, and Tellus Investment Partners LLP. In concert with the financing, the company announced that it successfully achieved an R&D milestone in its collaboration with Merck. That deal has a total potential value of $187 million plus royalties, and is one of three companies in BC with which Merck is working. Also in BC, and with offices in Princeton, NJ, Celator Pharmaceuticals closed a $6.4 million financing that included Thomas, McNerney & Partners, Domain Associates, Quaker BioVentures, Ventures West, Growthworks, and BDC. The company’s technology focuses on improving the efficacy of cancer treatments by optimizing the ratio of individual drugs in the treatment cocktail. Finally, Radient Technologies in Alberta raised $305,000 from two US investors. The company uses its patented Microwave Assisted Processing platform to extract compounds like alkaloids, glycosides, December 2012/ January 2013 BIOTECHNOLOGY FOCUS 21

Across Canada

$700

120

$600

100

$500

80

$400

60

$300

Deals (#)

Million ($CAD)

Venture Capital and Ins tu onal Investments in Private Canadian Life Sciences Companies

40

$200

20

$100

-

$-

Source: Techfinance, Lumira

160

$2,000 $1,800 $1,600 $1,400 $1,200 $1,000 $800 $600 $400 $200 $-

Venture Funding in Canada – Funds start to Flow

140 120 100 80 60

Deals (#)

Millions ($CAD)

Public Investments in Canadian Life Science Companies

40 20 -

Source: Techfinance, Lumira

Million ($CAD)

$60 $50 $40 $30 $20 $10 $0

60 50 40 30 20

Deals (#)

$70

Angel Investments in Private Canadian Life Science Companies

10 -

Source: Techfinance, Lumira

phenoloics, lipids, and terpenes from natural products.

Five publicly-traded companies raised only $6.8 million in Q3 2012, representing the lowest quarterly amount of capital raised in the Canadian public markets by biotechnology firms in at least 11 years. Medifocus closed a $3.3 million private placement with proceeds to be directed toward a relaunch of the company’s Prolieve device for the treatment of enlarged prostate, and to conduct a Phase 3 clinical trial for the company’s APA 1000 system. Medical software company Nightingale Informatix closed a $2.7 million convertible debenture round financed primarily by company insiders and angel investors. The company recently signed a deal to deploy its EMR to 22 BIOTECHNOLOGY FOCUS December 2012/ January 2013

3,500 healthcare providers in Ontario. Vancouver’s Functional Technologies closed the first $445,000 tranche of a private placement, and proceeds will be used to further commercialization of its yeast-based products for use in the food and beverage and healthcare industries.

Finally, Pyng Medical and Cynapsus Therapeutics raised $175,000 and $100,000, respectively, from company insiders for general working capital purposes.

Originally incorporated in Vancouver but now based in Austin, TX, XBiotech raised $7 million from angel investors, presumably to fund continued development of the company’s True Human antibody production platform. It should be noted that this one angel round for essentially a US-based company is more than the total capital raised by companies in the Canadian public markets during all of Q3. Finally, TheraVitae managed to raise $193,000 from undisclosed backers. The company markets a $54,000 stem cell therapy to patients for a range of cardiovascular disorders. Patients have to travel outside North America for the treatment as it has not been approved by regulatory authorities. One wonders how long it will be until the company shows up on in a 60 Minutes exposé similar to the recent piece on Stem Tech Labs.

New institutional fund formation in Canada has topped the $1 billion mark in Q3 2012, the largest in the past five years. Good news for a sector that has been hammered on the fund raising side for some years. To put this into perspective, we can look back a decade ago to 2001 at the height of enthusiasm for the venture asset class when pension funds, endowments, and other pools of managed capital invested over $2.6 billion in Canadian venture capital firms focused on information technology, life sciences, clean technology and other associated sectors.

Since its inception the venture capital industry has been primarily funded by institutional investors, including pension funds, corporate investors, family offices, endowments, and government funds. In addition, Canadian governments at both the federal and provincial level put in place tax incentives to facilitate the participation of retail investors into the venture asset class in the mid 1990s which was somewhat unique to Canada. This combination of tax incentives for capital formation, in parallel with an unprecedented technology boom, resulted in the rate of capital formation in the venture asset class throughout Canada increasing almost five-fold in the period from the mid-90s to 2001. Institutional investors, endowments, and retail investors alike sought to participate in what appeared to be the opportunity for outsized returns relative to other opportunities.

The disproportionate increase in capital from 1999 to 2003 produced a number of unfortunate results. As capital flowed into the venture ecosystem at unprecedented levels, new and inexperienced asset managers swarmed into the asset class. Moreover, the capital itself did nothing to increase the number of high-quality technologies, companies, or investment opportunities. In fact, it did quite the opposite. The pressure to deploy this additional capital within defined timeframes and regions resulted in investment managers pursuing investment strategies across a much broader range of sectors, business models, and management teams than had typically been supported by the venture capital ecosystem. In parallel with the dilution of high-quality investment opportunities, valuations skyrocketed as the supply of capital materially outpaced demand.

In many cases, even the very best and most sophisticated investors were essentially forced to pursue investments that only a few years earlier would have been dismissed on the basis of lack of manageContinued on page 24

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Across Canada Continued from page 22 ment team quality, innovation, competitive differentiation or proven business model, or on the basis of inflated valuation.

Fast forward to 2009 (post bubble and post 2008 economic down turn) and the amount of capital raised by institutional venture capital funds was a mere $146 million. The Canadian experience has been much like that of the United States, where overall VC returns have also been inversely related to capital formation (over a certain level of committed capital) and where returns for the class as a whole have declined for much of the past 10 years. The one notable difference in the US is that the top quartile of experienced and well-positioned managers was able to continue to deliver the returns expected of the asset class. With less experience, maturity and depth within the venture ecosystem, the problems in Canada were exacerbated by the introduction and rapid expansion of labour-sponsored investment funds, which used federal and provincial tax incentives to induce unsophisticated retail investors to invest in venture capital funds.

Over the past few years several new initiatives across the country were put into place to help re-energize the ecosystem. This has led to institutional and government supported limited partners being able to announce a string of new commitments this year (and last).

So what does this mean for the biotech sector? Well it means a fundamental change from the five-year period prior to last year when no new institutional money was raised in the life sciences sector.

Over the last 12 months, four significant funds were formed: Lumira Capital announced two new funds with total commitments of $149

innovator

Jacki Jenuth, is Prinicipal with Lumira Capital , a leading Canadian life sciences venture capital manager.

To see this story online visit http://biotechnologyfocus.ca/?p=3043

T The Prrocess

Continued from page 17 carbonic anhydrase and even with certain energy efficient solvents, the scrubber column in this model would need to be 600 metres tall, whereas ours is only 30 metres. The enzyme reduces the size of the structure required, so your capital costs come down significantly. The introduction of the enzyme allows for the use of far less solvent, requiring less energy to regenerate, so operational cost drops by as much as 40 per cent. Overall, these factors bring carbon capture well within an affordable range.”

In November 2012, the clean tech company was awarded $500,000 in funding from Alberta’s Climate Change and Emissions Corporation (CCEMC) for pilot testing in the Alberta Oil Sands The 12-month project will see CO2 Solutions’ technology adapted for the efficient capture of carbon dioxide emissions from oil sands production, the fastest growing source of carbon emissions in Canada.

“The reason CCEMC was put into place was to advance technologies that will allow industry to reduce its costs for carbon management and carbon capture. That’s exactly our mission in life,” says Kelly. “So for us, it’s a very strong validation of the potential of our technology.”

In terms of other future projects, Kelly sees

million from corporate partner Merck, Teralys Capital, BDC, Fonds de solidarité FTQ and several other investors; TVM Life Science Ventures VII closed on $150 million with LP’s that include Teralys Capital, corporate partner Eli Lilly, BDC Venture Capital, Fondaction and Advantus Capital Management; GSK Canada announced a $50 million commitment to its internal venture group that will target Canadian venture opportunities exclusively; and Avrio Ventures closed a $90 million ag-tech fund with commitments from Farm Credit Corp. and Aimco.

We remain supportive of initiatives at both the federal and provincial level that are dedicated to re-energizing the venture ecosystem in Canada. Further, we would encourage governments to continue implementing strategies that facilitate the entry of other value-added players into the venture ecosystem, including pension funds, endowments, corporations and fund-of-funds which are critical in providing capital to VCs who deploy capital, build value, and ultimately create jobs and wealth for Canadians.

© 2012 CO2 Solutions. All rights re eserved.

the company’s technology being applied to more conventional, non-regulatory driven industries such as natural gas sweetening, chemical and ammonia production, and other smaller economically driven applications.

As for policy-driven large-scale emitters, in the future Kelly anticipates more regulation for emissions, with 2015 as the tipping point where industry will start installing the equipment to manage their carbon dioxide emissions.

“In Canada we have pretty ambitious federal government targets, to reduce emissions

24 BIOTECHNOLOGY FOCUS December 2012/ January 2013

17 per cent by 2020,” says Kelly. “To get there, we’ll need regulation. If we’re ever going to meet those targets, we’re going to have to start managing our emissions on a much larger scale than we’re doing now.”

Whether we hit this target or not, only time will tell. But CO2 Solutions is certainly poised to be a big part of the effort.

To see this story online visit http://biotechnologyfocus. ca/?p=3038

By Nathalie Richard

Opinion

Fostering Great Leadership As part of my work, I am often asked about what makes a company successful.

Although there are many factors, one consistently tops all others.

Although there are many factors, one consistently tops all others. Leadership. Jim Collins highlights in his book, Good to Great, that great companies are often driven by Level 5 Leaders—Leaders that not only exceed through skill and competence, but that also exhibit a blend of personal humility and professional will. I can echo Jim’s findings through my work with over 150 life science companies in Ontario.

I have seen the impact of Level 5 Leaders in transforming good companies into outstanding ones. I thought that I would take this opportunity to reflect upon what it takes to become a Level 5 Leader and how we can foster their development. There are no right answers, rather my reflections are meant to start a conversation as we look at leadership through the different lenses of our experiences and perceptions.

I recall someone once defining leadership as “lead-our-ship.” It is a definition that I appreciate as it captures the very essence of a true leader: the desire to tackle complex challenges, to build, create and contribute to an organization’s success by enabling individuals with different perspectives and experiences to move toward common goals.

Yet, the development of strong leadership competencies begins with a passion for your field. As I look back at my transition from health care to finance and my ongoing professional development, one factor has consistently held true. I have always worked in a space for which I have a great passion. It is what Keith Farrazzi calls the “Blue Flame,” the intersection of your passion and your abilities. Passion and skills alone, however, are not sufficient. Level 5 Leaders must also possess a great deal of ambition directed towards challenging the status quo and building long-term successful organizations.

Becoming a Level 5 Leader starts with a passion for your field. It then requires the alignment of both personal and professional desires to continuously challenge the status quo, seek out leadership opportunities and build sustainable organizational successes.

We often associate today’s leadership to larger than life personalities, and as result, we struggle to recognize our everyday Level 5 Leaders. Yet, we have no shortage of them.

The problem lies in our belief that leadership equates with high profile leaders. As Jim Collins remarks, Level 5 Leaders are a far cry from the “egocentric celebrit[ies].” Though highly driven individuals, Level 5 Leaders channel their ambitions through personal will and humility, choosing to highlight everyday leadership rather than cultivating celebrity status.

Another key challenge is for individuals to self-identify as potential leaders. In order to capture the benefits of their hard-earned efforts, future leaders need to understand and believe in their own successes. These successes start early on with small leadership opportunities where one can learn to motivate and guide others, and progress to more complex challenges which impact broader organizational dynamics. The role that is played by colleagues and mentors in allowing individuals to identify leadership skills and opportunities are crucial to the development of a future leadership base.

According to Judith Elder, the former general manager Microsoft Canada Consumer Products Division, organizational leadership not only requires a desire to lead complex organizations, but also that others be ambitious for you. The people that work with you and for you must believe in your ability to help them achieve their goals and those of the organization.

I am extremely lucky in my life to have parents, colleagues and mentors that support my personal ambitions and encourage me to keep pushing the boundaries of what I can accomplish. They are my guides and my cheerleaders; they have provided me with the opportunities to lead and the support to pursue my journey. I plan on passing along the lessons that I learn to my own mentees so that they too can develop their true leadership potential.

In closing, successful companies exhibit many attributes. The one common factor is great leadership. Becoming a Level 5 Leader starts with a passion for your field. It then requires the alignment of both personal and professional desires to continuously challenge the status quo, seek out leadership opportunities and build sustainable organizational successes. Nevertheless, personal ambition must be reinforced by the celebration of everyday leadership and the support of your ambitions by those close to you.

Fostering the development of more Level 5 Leaders will help us transform more organizations from Good to Great.

To see this story online visit http://biotechnologyfocus. ca/?p=2449

December 2012/ January 2013 BIOTECHNOLOGY FOCUS 25

NEW PRODUCTS Sequencing The SPRIselect from Beckman Coulter Life Sciences utilizes SPRI-based (solid phase reversible immobilization) chemistry to speed and simplify genomic DNA size selection for next generation sequencing fragment library preparation. Following shearing, the library construction process requires size

ture, set digitally, is accurate to a tenth of a degree and ensures effective and gentle incubation. State-of-the-art rotary pushbutton input and graphic LCD display are used to easily set the most demanding programs in English, French or Spanish. The controller accommodates up to 10 different users, each having up to 10 stored programs. The controller’s USB interface can be used to transfer data to a PC for BINDER APT-COM™ software analysis.

Gas controller Warner Instruments introduces its Bold Line CO2 Controller, part of the complete line of gas controllers from Okolab. The Bold Line CO2 controller mixes air or N2 and CO2 and controls the

Web: www.binder-world.com

selection to produce uniform distribution of fragments. SPRIselect allows size distribution to be adjusted between 150 and 800 base pairs to suit the application and sequencing platform. The process can be performed manually or can be automated for high throughput in 96-well plates on platforms such as Beckman Coulter Life Sciences’ Biomek workstations. SPRIselect reagent kits are available in 5, 60 and 450 mL volume, and come with guidelines to assist users in customizing protocols. Gel cartridges, chips and additional instruments are not needed.

Web: www.beckmancoulter.com Refrigerated incubator The new Binder Inc. KT 115 refrigerated incubator utilizes Peltier refrigeration technology to provide secure, accurate control. With comprehensive program functions, the unit offers a wide range of capabilities for incubating biological materials. Functional chamber volume is 3.7 cu.ft. (104 litres), and the unit can run at temperatures down to 4°C. The incubator’s APT.lineTM preheating chamber technology ensures homogenous temperature conditions, as well as rapid heating and recovery times. Horizontal airflow from both sides of the chamber provides uniform temperature distribution, even when the unit is fully loaded. Tempera-

Chromatography GE Healthcare’s ÄKTA™ pure, is a chromatography system for purification of proteins. ÄKTA pure is easy-to-use and can support both routine and challenging purification requirements, as well as being adaptable to changing research needs. ÄKTA pure is specifically designed to enable researchers - from beginners to experts - to easily isolate their target protein, whether under simple or complex conditions. With the addition of simple drag-and-drop method templates in the UNICORN™ 6 control software it is also possible to electronically track the use of, and data obtained from, individual columns, which is particularly useful as chromatography systems are often placed in shared facilities.

Web: www.gelifesciences.com/akta Counter The Scienceware® Colony Counter is a simple to operate device that can count colonies of bacteria or other microorganisms grown on an agar plate.

It marks, counts, and gives an audible and visual alert each time a count is registered on the digital display. Its lightweight, comfortable to hold, pen-style design reduces the likelihood of error, combining all aspects of counting into one motion.

Error is further reduced by the ability to count both up and down to verify sample counts. Able to store up to 35 sample counts in its memory, it can also display the sum total of all colonies counted. The display has a backlight for easy viewing in low light conditions; the audible alert can be turned off if desired; and the counting function can be locked to prevent error during breaks between counting.

Web: www.belart.com 26 BIOTECHNOLOGY FOCUS December 2012/ January 2013

gas concentration with digital accuracy.

Mix CO2 from 0 to 18 per cent concentration with an accuracy ± five per cent of the concentration. Set point resolution is 0.1 per cent. The instrument is easily operated via a touch screen interface, OKO-Control 2.0 software, or Nis Elements software. The controller can be attached to an O2 Unit-BL [1-20] to control both CO2 and O2 within the range 0 to 10 per cent and 0 to 18 per cent respectively. An optional smart box data logger and web server allows operation via any webenabled device. Sensor calibration is made with an external meter or calibration gas.

Web: www.warneronline.com Incubator Sheldon Manufacturing, Inc. introduces the SHEL LAB Model 2428H, the newest addition to its large capacity CO2 incubator line. This 27 cubic foot incubator features active humidity control up to 95 per cent. Compared to water pan humidity generation, the 2428H humidity system provides less evaporation of culture media and eliminates a potential source for contamination. The 2428H also has a heated glass door that minimizes condensation, another potential source for contamination. The triple-paned glass door allows easy viewing of samples without having to open the incubator door, so samples can thrive in the stable environment within the chamber. The incubator also features an antimicrobial copper drain and uses a gentle horizontal air flow heating system to obtain temperature uniformity and quick temperature recovery after door openings.

Web: www.shellab.com.

NEW PRODUCTS Gas Chromatography Thermo Fisher Scientific Inc. has added negative and positive ion chemical ionization (CI) capabilities to its new Thermo Scientific TSQ 8000 triple quadrupole GC-MS system. The addition of chemical ionization to the TSQ™ 8000 GC-MS/MS increases analytical options available to the user for addressing the diverse challenges of complex, trace level analysis. Chemical ionization can be used

Sample handling Chemists gain a whole new perspective on sample handling with Vista Vial™ series chromatography vials from J.G. Finneran Associates. The patented, two-part design consists of a glass base and a polyethylene top that snaps together to form a standard 12x32mm auto sampler vial. The glass base provides a wide target for pipettes and is ideal for highly viscous and foaming samples. The polyethylene top is available with 8 to 425mm threaded, 9mm threaded or 11mm Snap Seal™ neck finishes offering chemists a choice of closure systems. Depending on

the sample, disposal of vials is easier as the plastic can be incinerated intact without the need for closure removal. The Vista Vial™ 1.0mL volume glass base is constructed of Type 1 borosilicate glass in either clear or amber. The polyethylene top accommodates 8-425mm standard and 9mm R.A.M. screw thread closures and septa. Threaded closures and septa are available individually or preassembled. The Vista Vial™ with 11mm Snap Seal™ finish accepts J.G. Finneran Poly Crimp™ seals, Snap Top Caps™ and standard aluminum seals.

Web: www.jgfinneran.com

SRC101

for applications such as persistent organic pollutants (POPs), and methods that utilize halogenated derivatized reagents including estrogenic compounds or tetrahydrocannabinol (THC) in hair. In addition to the CI capability, Thermo Fisher also introduces direct insertion and direct exposure probe options, which further enhance the user’s ability to analyze samples in the TSQ 8000 mass spectrometer. These options are especially useful in combination with MS/ MS for applications such as the rapid structural characterization of chemical reaction products, which are important in chemical research and academic applications.

Web: www.thermoscientific.com Cell Imaging Andor Technology plc has launched its latest spinning disk confocal device, the Revolution WD for live cell confocal imaging. Taking a leap forward by offering four times the field of view, along with a new design for imaging at low and high power magnifications, the Revolution WD offers confocal images for larger samples as well as small. This new spinning disk confocal device offers a broad user base, appealing to new fields such as neuroscience, developmental biology, stem cell research, embryology and intra-vital imaging.

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CALENDAR December 2012/ January 2013 December 15-19 ASCB 52nd Annual Meeting Venue: San Francisco, CA Tel: 301-347-9300 Fax: 301-347-9310 Email: ascbinfo@ascb.org Web: www.ascb.org

JANUARY 2013 January 7-9 Biotech Showcase™ 2013 Venue: San Francisco, CA Tel: +1 760 930 0500 Email: jgriego@ebdgroup.com Web: www.ebdgroup.com/bts/index.php

January 12-16 SLAS 2013 Venue: Orlando, FL Tel: 630-256-7527 Fax: 630-741-7527 Email: slas@slas.org Web: www.slas2013.org

January 20-24 11th Winter Conference on Medicinal & Bioorganic Chemistry Venue: Steamboat Springs, CO

Tel: +44-1435-873062 Email: claire@scientificupdate.co.uk Web: www.mbcfconference.com/events/ wmbcf-next-event-2013.html

January 26-29 2013 Annual Meeting of the ORS Venue: San Antonio, TX Tel: 847-823-5770 Fax: 847-823-5772 Email: ors@ors.org Web: www.ors.org/

Venue: Vancouver, BC Tel: 604.601.8372 Fax: 604.689.4486 Email: contact@techvision.com Web: www.techvision.com/bpn/

March 2013 March 11-13

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BIO-Europe Spring Venue: Barcelona, Spain Tel: 760-930-0500 Email: chundschell@ebdgroup.com Web: www.ebdgroup.com/bes/index.php

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March 17-22

BIO CEO & Investor Conference Venue: New York, NY Email: bd_registration@bio.org Web: www.bio.org/events/conferences/ bio-ceo-investor-conference

PITTCON Venue: Philadelphia, PA Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org

February 22-24 2013 BIOTECanada Whistler Meeting on the Mountain and CEO Summit Venue: Whistler, BC Email: kira.pejemsky@biotech.ca Web: www.biotech.ca/en/ what-we-do/2012events.aspx

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April 2013 April 22-25 Bio International Convention Venue: Chicago, IL Email: reg2013@bio.org Web: www.convention.bio.org

11th Annual BioPartnering North America

Company & Advertiser Index COMPANY Page Website AlbertatBay...............................................................................................................25...........................................................................................www.albertatbay.com Allon Therapeutics Inc.................................................................................. 6.........................................................................www.allontherapeutics.com Andor Technology plc.................................................................................. 27.......................................................................................... www.andor.com AstraZeneca Canada..................................................................................... 8..................................................................................... www.astrazeneca.ca Beckman Coulter Life Sciences.................................................................... 26..........................................................................www.beckmancoulter.com Belart........................................................................................................... 26.......................................................................................... www.belart.com Best Western Victoria Park Suites.........................................................................25..........................................................................................www.victoriapark.com Bioniche Life Sciences Inc............................................................................. 6.......................................................................................www.bioniche.com Biopartnering North America...............................................................................13..................................................................................www.techvision.com/bpn/ Canadian Government Executive.........................................................................3.............................................................................www.cgeleadershipsummit.ca Children’s Miracel Network....................................................................................9.......................................................................www.ChildrensMiracleNetwork.ca Eppendorf.................................................................................................................32............................................................................ www.eppendorcomplete.com GE Healthcare.............................................................................................. 26............................................................................. www.gelifesciences.com Mitomics Inc................................................................................................ 10................................................................................www.mitomicsinc.com NEOMED Institute......................................................................................... 8...........................................................................................www.neomed.ca Pfizer Canada................................................................................................ 8............................................................................................... www.pfizer.ca POI..............................................................................................................................31.............................................................................................................. www.poi.ca Sheldon Manufacturing Inc.......................................................................... 26........................................................................................ www.shellab.com Tekmira Pharmaceuticals Corp.................................................................... 10.............................................................................www.tekmirapharm.com Thermo Fisher Scientific Inc......................................................................... 26..........................................................................www.thermoscientific.com VWR.............................................................................................................................2...............................................................................................https://ca.vwr.com/ Warner Instruments..................................................................................... 26.............................................................................. www.warneronline.com 28 BIOTECHNOLOGY FOCUS December 2012/ January 2013

ThE LAsT WoRd

By Robert Foldes

Improving Investor Confidence Amidst

CLINICAL FAILURES:

IS IT TIME TO RETHINK OUR APPROACH TO DRUG DISCOVERY?

Robert Foldes is Managing Partner of Cognovie Inc. and can be contacted at Robert@cognovie. com

“For every problem there is a solution which is simple, or internally developed, without demonstrating a high clean and wrong.” affinity and “specific” interaction with a well characterThis quote attributed to H.L. Mencken, the American ized protein target. This focus involves optimizing for journalist known as the “Sage of Baltimore,” dominated nanomolar potency against the target, even though this much of my thinking since I first stumbled upon it in potency does not predict biological efficacy. An increasgraduate school. I would draw on this concept in every ing volume of evidence suggests that many drugs derive seminar and hallway conversation to challenge my col- their therapeutic benefit from interactions with multiple leagues and fellow scientists to gain new perspectives to analyze their research endeavors. In those days of reduction“The pharmaceutical industry is still trapped ism, it was all too easy for molecular in the traditional paradigms of reductionism” biologists and biochemists to focus on genes or proteins of interest and lose sight of the immense complexity (and redundancy) inher- proteins rather than a single target. ent in all biological systems. Of course, scientific research Notwithstanding rational drug design, every drug will has evolved tremendously over these past 20 to 30 years. interact in varying degrees with unknown or unintended “Systems biology” has now developed into an interdisci- biological targets. And despite scientific advances, there plinary field of study that focuses on complex interactions are no models in current use that can accurately predict within biological systems using a more holistic approach. safety and efficacy in humans of a new chemical entity Researchers are currently using these approaches to or biological entity with a novel mechanism of action, no model properties of cells, tissues and organisms. matter how well it has been characterized in cell-based One might argue that the pharmaceutical industry is or animal models. This is the chief failing of reductionist still trapped in the traditional paradigms of reductionism. approaches to drug discovery that are likely largely acVery few (if any) drug candidates are externally sourced, countable for the continuing slide in clinical trial success December 2012/ January 2013 BIOTECHNOLOGY FOCUS 29

THE LAST WORD

rates. It is now estimated that 30 preclinical programs are needed to produce a single new drug.

A favourite approach of the industry to increase clinical success has involved reformulation or repurposing of marketed drugs. Another approach has been to focus on chemistries and mechanisms that have already yielded market-validated drugs (this would also include “biosimilars”). However, regulators and payers continue to raise the bar on so-called “me-too” drugs, limiting the long-term viability of these strategies.

As Matt Ridley wrote in the Wall Street Journal last year, “…the goal of most pharmaceutical research – identifying a “target” for drug action – is misconceived” since “biochemical networks are designed to work around the loss of any one node.” He suggests that “drugs must be designed to nudge whole networks rather than single

“An increasing volume of evidence suggests that many drugs derive their therapeutic benefit from interactions with multiple proteins rather than a single target” targets” meaning “hitting multiple targets simultaneously.”

These targets can be informed by network analysis or systems biology. And certainly in agreement with H.L. Mencken, effective cures must be tailored to reflect the complexity of the disease.

The oncology field has realized for some time that there are powerful synergies through multiple interventions within a complex biological network. These are manifested in combination chemotherapeutic regimens involving “single-target” drugs. These regimens may arise through serendipity or “trial-and-error” approaches. However, the high-level of toxicity usually associated with individual cancer drugs introduces many challenges in designing tolerable combination regimens. Hopkins et al. (Current Opinion in Structural Biology 16: 127-136, 2006) discuss how it might be possible to rationally design promiscuous drugs by combining advances in chemoinformatics and structural biology. Another approach may involve reexamining chemical compounds shown to be associated with beneficial health outcomes or biological activities but not previously developed into drugs due to lack of target specificity. Natural products derived from plants provide a rich resource of such chemical knowledge.

One example of a promiscuous compound that displays polypharmacology is epigallocatechin-3-gallate (EGCG) an abundant component of green tea. As many of us know, green tea consumption has been associated with reduced risk of developing certain cancers. A large volume of scientific literature has demonstrated the anti-tumour properties of EGCG in animal models in the absence of significant toxicities. EGCG has been shown 30 BIOTECHNOLOGY FOCUS December 2012/ January 2013

to directly inhibit chymotrypsin-like proteasome activity (at submicromolar concentrations) while also affecting (but likely at lower affinities) important other cancer targets such as mTOR, PI3Kα, AMPK and others. The attraction of EGCG as a drug candidate has been limited by its relatively low bioavailability and lack of composition of matter patent protection. However, analogs and derivatives of EGCG have been designed that address these issues and furthermore provide enhanced biological potency. In this case, the risk of failure due to safety issues would be relatively low. Similar to any other drug candidate, selecting the optimal dosing regimen and patient population is critical, although in this case one would be informed by many years of human experience with green tea consumption. Compounds like EGCG that affect multiple pathways of importance for disease intervention while maintaining a good safety profile provide new approaches to reduce clinical risk and hope to ultimately restore investor confidence in the sector.

After writing this article, I became aware of an excellent paper by Scannell et al. (Nature Reviews Drug Discovery 11, 191-200, 2012) that reinforces and expands on several points I raise above. I welcome your comments and feedback.

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To see this story online visit http://biotechnologyfocus.ca/?p=3045

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