Biotechnology Focus November 2013 by Promotive Communications

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

NOVEMBER 2013 VOLUME 16, NUMBER 9

CELL THERAPIES THE IMPORTANCE OF UMBILICAL CORD BLOOD BANKING

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LIFE SCIENCE IS A HUMAN RACE 78% of global CEOs rank human capital as the #1 priority*

Making the next breakthrough isn’t about luck. It’s about talent, pure and simple. The brightest minds, specialized education, the insatiably curious – all blended in this unique sector of the knowledge economy. The race is always on in Life Sciences, and Mississauga, Ontario – Canada, is where great companies build winning teams. What else do you need to know?

VISIT WINTHEHUMANRACE.CA TO START NOW. *Source: PwC 15 th Annual Global CEO Survey 2012

contents NOVEMBER 2013 – VOLUME 16 – NUMBER 9

Bereskin & Parr’s Noel Courage discusses biosimilar patent enforcement in Canada

FEATURES THE IMPORTANCE OF UMBILICAL CORD BLOOD BANKING In light of the announcement that the Canadian Public Cord Blood Bank is starting to collect in Ottawa, Ian Rogers discusses UCB banking, private and public banks and the latest indications and discoveries for UCB cells (By Ian Rogers)

Canada’s awash in biofuels Opinion

BIOSIMILAR PATENT ENFORCEMENT IN CANADA Reviewing NOC regulations as well as conventional patent options that apply in proceedings involving biosimilars (By Noel Courage)

DEPARTMENTS 6

RESEARCH NEWS

BUSINESS CORNER

IN EvERY ISSUE

26 NEW PRODUCTS

28 CALENDAR OF EVENTS

8 RESEARCH NEWS

McMaster lab develops new tuberculosis vaccine

www.biotechnologyfocus.ca

OPINION Commentary on why new approaches to manage cancer are desperately needed (By Robert Foldes)

INNOVATOR Spotlighting Stem Cell Therapeutics Inc., and how this immunotherapy and cancer stem cell company is getting at the root of cancer (By Shawn Lawrence)

THE LAST WORD Checking the pulse of Canada’s regenerative medicine industry (By Michael May)

November 2013 BIOTECHNOLOGY FOCUS 3

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PUBLISHER’S NOTE

PUBLISHER/ EDITOR-IN-CHIEF SENIOR WRITER STAFF WRITER CONTRIBUTING WRITERS

Québec invests big The Québec government recently announced $3.7 billion in funding for research and innovation. To be doled out over the next five years, the financing is a promising first step for revitalizing biopharma in Québec. It also fits into Québec’s overarching goal to focus more on partnerships and collaboration in the life sciences. The $3.7 billion is a part of the government’s new National Research and Innovation Policy (PNRI). The new policy has a number of key investments, including funding for bio-based organizations in Québec and private-public partnerships. It aims to improve Québec’s knowledge-based economies and encourage collaboration across disciplines. Much of the earmarked money will go towards the province’s academic sector, with investments in universities, colleges and some funding for laboratories in public high schools. The organizations getting funded include the Fonds de recherche du Québec, Génome Québec, NanoQuébec and Calcul Québec. Financing was also allocated for creating the FondsInnoMonde, set to promote international partnerships and to further the province’s strategy in becoming a leader in personalized healthcare. Personalized healthcare plays a large role in the new R&I strategy. Since the beginning of this year, over $110 million has been invested in Québec for personalized health care research partnerships. The Québec government is expected to announce a number of projects under the Fonds de partenariat pour uninnovant et en santé which will translate into $250 million in public-private investments for personalized health care. These investments will be supported by the new PNRI, and confirm that personalized health care is a growing sector of excellence in the province. Along with improving health care, part of the new strategy’s aim is to offer financial and technical assistance to SMEs wishing to apply for a first patent. To funnel new talent into the life sciences, it’s also launching a program to help college and university grads get their first job in research. The return to financing for academics is a hopeful first step.The Québec government faced much criticism for not providing enough funding last year for academics and researchers. This new funding goes a long way towards making amends for those budget cuts. Some are even holding out hope that more is still to come. Many in the province, especially those in the biopharmaceutical industry, feel that more support for the private sector is needed, and that this policy didn’t provide enough funds for industry. Overall however, the investment outlines promising targets for Québec’s research and innovation. And if Québec is able to meet these targets, it’s well on its way to becoming an unrivaled spot for the life sciences. Have any thoughts or comments about the recent funding announcement? Let me know at biotechnology_focus@promotive.net.

Terri Pavelic Shawn Lawrence Daniela Fisher Ian Rogers

Julie Desrosiers

Mélanie Bourassa Forcier

Michael May

Noel Courage

Robert Foldes

National Account Manager GRAPHIC DESIGNER CONTROLLER MARKETING MANAGER

Marcello Sukhdeo Elena Pankova John R. Jones Mary Malofy

CIRCULATION DIRECTOR 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, AdFarm; Ulli Krull, UTM; John Kelly, KeliRo Company Inc.; 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

4 BIOTECHNOLOGY FOCUS November 2013

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R & D NEWS Canada’s first clinical genomic centre for children

Clinical Trials & Patents Mimetogen Pharmaceuticals Inc. (Montréal, QC) has commenced patient enrollment in its first Phase 3 clinical study of MIM-D3 ophthalmic solution for the treatment of dry eye syndrome. MIM-D3 is part of a class of molecules called TrkA agonists and it stimulates the production of mucin, which plays a critical role in the protection and overall health of the ocular surface. Mucins are essential for lubrication; the removal of allergen, pathogens, and debris; and corneal epithelial healing to reduce ocular surface damage. Mimetogen believes, MIM-D3 may have additional benefits than currently available dry eye therapies, including the potential to improve neural function, which may improve corneal sensitivity and integrity. The Phase 3 trial will further evaluate the safety and efficacy of MIM-D3. Approximately 400 patients will be randomized to receive one per cent MIM-D3 ophthalmic solution or placebo twice daily over an eight week period. The primary endpoints of the study are corneal fluorescein staining score in the CAESM and ocular dryness. The safety and comfort of MIM-D3 compared to placebo will also be evaluated.

A photo of SainteJustine UHC, where the new genomic centre will be located. Canada’s first integrated clinical genomic centre in pediatrics will open its doors in Québec. The new centre is located at Sainte-Justine UHC, the largest motherchild university hospital centre in Canada. Created in collaboration between SainteJustine UHC and Génome Québec, the new centre will help develop new solutions for the challenges involved in diagnosing children with genetic diseases. The initiative aims to transform the quality of care available for young patients and to improve prevention efforts from early childhood. “Over 80 per cent of genetic diseases are diagnosed in childhood or adolescence,” said Dr. Jacques L. Michaud, a doctor and geneticist at Sainte-Justine UHC. “In more than half of these children, doctors are unable to arrive at a diagnosis, and many years go by before the cause of the disease is identified. With this new technology, we can sequence all the genes of a child’s genome, develop a genetic profile in a timely manner, establish a diagnosis and deliver the treatment, if one is available at the time or becomes available in the future. A parent’s worst nightmare is not knowing.” Sainte-Justine UHC is known for its leading laboratory for genetic analysis in children. As part of the initiative, the Sainte-Justine UHC team will be in charge of developing strategies for interpreting results, producing reports and validating clinical data. “Our mission is to improve the health of mothers and children in Québec, and with this genomic centre, we can offer them better diagnostic approaches and

6 BIOTECHNOLOGY FOCUS November 2013

therapies to do just that,” said Dr. Fabrice Brunet, CEO at Sainte-Justine UHC. “We will be able to take treatment of pediatric diseases to the next level, whether we are talking about acute illnesses such as cancer, chronic diseases such as diabetes or neuro-developmental disorders. The technology will also help us diagnose diseases more quickly in a larger number of children and at a lower cost.” Génome Québec will spearhead the operation of the platform, including sequencing and bioinformatics analyses. “This is the moment we have been waiting for. Genomic technology has now reached the point where, in the very near future, it will be used to treat patients living with genetic diseases, not to mention prevent and screen for diseases to improve public health,” explained Marc LePage, president and CEO of Génome Québec. He adds that the partnership signals an important shift toward personalized health care. “It is a stepping stone that will pave the way for future initiatives in other areas, for example, complex diseases.” The partnership is the latest in a number of major investments made by the Government of Québec in the field of personalized health care.The new genomic centre will also offer services to Canadian and international markets. With more international exposure, the collaboration hopes to establish Québec as a global leader in clinical genomics for pediatrics and personalized health care. To see this story online visit http://biotechnologyfocus.ca/?p=9496

Angiochem (Montréal, QC) has released complete analysis results of its Phase 2 clinical study with ANG1005 (a paclitaxel-peptide drug conjugate) in breast cancer patients with brain metastasis. The data, which includes the complete intent-to-treat (ITT) analysis, demonstrated promising signs of anti-tumour activity. Angiochem presented the Phase 2 ITT analysis with ANG1005 in 80 HER2-positive and HER2-negative breast cancer patients with brain metastases. Two doses, 650mg/ m2 (n=13) and 550mg/m2 (n=67), were evaluated for intracranial anti-tumour responses including response rate, progression-free survival (PFS) and overall survival (OS), as well as safety and tolerability. In the study, ANG1005 was generally safe, well-tolerated and demonstrated an adverse event profile consistent with conventional taxane therapy in both HER2-positive and HER2-negative cohorts at both dose levels studied. In addition, patients in both the HER2-positive and HER2-negative populations experienced anti-tumour responses including up to 14 patients with intracranial partial responses (PR), 35 patients with stable disease (SD) and six months overall survival in up to 85%. Based on these results, Angiochem will advance ANG1005 into further clinical development including a Phase 2 clinical study in patients with recurrent high grade gliomas and a second Phase 2 study in HER2positive breast cancer patients with brain in 2014.

For more R&D news visit http://biotechnologyfocus.ca/ category/bio-pharma/

R & D NEWS

Dr. Peter Zandstra

Researcher behind Canadian stem cell technology recognized with Till & McCulloch Award

A Canadian technology that has the potential to boost the number of stem cells given to patients undergoing transplants of the blood-forming system has been recognized as the most impactful stem cell research paper authored by a Canadian in the past year. For his work, Dr. Peter Zandstra has been given the 2013 Till & McCulloch Award. Dr. Zandstra accepted the award and presented a lecture entitled “Engineering pluripotent stem cell derived microtissues” as part of the Till & McCulloch Meetings, Canada’s premier stem cell event held last month AdAB. (Final):Layout 1 12-05-14 5:13 PM inOBIO Banff,

The author of the research paper Elizabeth Csaszar, along with Dr. Zandstra and his team have developed a new culture system that has the ability to dramatically expand the clinical applications of hematopoietic (blood) stem cells (HSCs). Their discovery is based on a Fed-Batch bioreactor technology and has the potential to improve the viability and success of cord blood stem cell transplantation by allowing for better-matched donors and increasing the number of stem cells in a transplant unit. The new system has the potential to accelerate the possibilities of using HSC transplantation in clinical settings, especially in the treatment of certain forms of leukemia as the success rate of blood system transplantation is strongly correlated to the number of cells used. Dr. Zandstra’s Fed-Batch technology can produce over 11 times more HSCs than originally existed and is designed to be adaptively scaled-up for human transplantations in clinical settings. The article for which the award was granted, published in the February 2012 isPage 1 Cell Stem Cell, entitled “Rapid Expansue of

sion of Human Hematopoietic Stem Cells by Automated Control of Inhibitory Feedback Signaling,” explains this novel discovery to expand cord blood cells. Dr. Zandstra is a professor at the University of Toronto’s Institute for Biomaterials & Biomedical Engineering, a principal investigator with the McEwen Centre for Regenerative Medicine and the CSO at the Centre for Commercialization of Regenerative Medicine. Dr. Michael Rudnicki, scientific director of the Stem Cell Network, who launched the Till & McCulloch Award in 2005 and presented the award, says the Zandstra group’s publication was chosen due to the impact their technology is expected to have. “This technology will hasten the promise of regenerative medicine and the therapeutic possibilities of umbilical cord blood and hematopoietic stem cells in particular. It is very likely that Fed-Batch technology will improve the outcome of blood system transplants for many patients.” To see this story online visit http://biotechnologyfocus.ca/?p=9277

Ontario Bioscience Innovation Organization

OBIO™ members lead innovation in the life sciences. Every facet of health care with a stake in innovation is represented on OBIO Advisory Boards. Together, we’re building a bioscience cluster that nurtures and promotes development of innovative products and services to meet the health needs of growing Canadian and global markets. Ontario Bioscience Innovation Organization is a trade name of Ontario Bioscience Industry Organization.

November 2013 BIOTECHNOLOGY FOCUS 7

R & D NEWS McMaster lab develops new tuberculosis vaccine

A tuberculosis vaccine developed at McMaster University may offer new hope for the global fight against tuberculosis. “We are the first to have developed such a vaccine for tuberculosis,” said Dr. Fiona Smaill, professor and chair of the Department of Pathology and Molecular Medicine of the Michael G. DeGroote School of Medicine at McMaster. She led the phase one clinical study published in the journal Science Translational Medicine. The vaccine, based on a genetically modi-

fied cold virus, was developed in the lab of Zhou Xing, professor of pathology and molecular medicine and the McMaster Immunology Research Centre, who co-led the phase one study. Both Drs. Smaill and Xing are also members of the Michael G. DeGroote Institute for Infectious Disease Research. “Tuberculosis is a serious public health threat,” Smaill said. “One-third of the world’s population is infected with the organism that causes tuberculosis, and it remains the top infectious killer of people only secondary to HIV; yet, the current vaccine used to prevent it is ineffective.” She adds that the control of tuberculosis (TB) has met with further challenges from high incidence of multi-drug resistant tuberculosis. The new vaccine was developed to act as a booster to Bacille Calmette Guerin (BCG), currently the only TB vaccine available. BCG was developed in the 1920s and has been used worldwide. The new “booster” would reactivate immune elements that over time diminish following BCG vaccination.

The McMaster vaccine has been more than a decade in the making. McMaster researchers began the first human clinical trial in 2009 with 24 healthy human volunteers, including 12 who were previously BCG-immunized. “The primary goal was to look at the safety of a single dose vaccine injection,” said Xing, “as well as its potency to engage the immune system.” By 2012 they established that the vaccine was safe and observed a robust immune response in most trial participants. More clinical trials are needed to measure the vaccine’s real potential, Xing comments. The development of the McMaster vaccine was supported by the Canadian Institutes of Health Research, Canadian Foundation for Innovation, World Health Organization, Ontario Ministry of Research and Innovation, McMaster University, and the Michael G. DeGroote Institute for Infectious Disease Research. To see this story online visit http://biotechnologyfocus.ca/?p=9384

CDRD partners with Dalhousie and IWK Health Centre to establish new Atlantic Node The Centre for Drug Research and Development (CDRD), Dalhousie University and the IWK Health Centre have come together to establish a new CDRD Atlantic Research Node to enhance CDRD’s drug development infrastructure. This CDRD Atlantic Node will initially be focused on zebrafish models of disease, leveraging the knowledge, expertise and infrastructure of Dr. Jason Dr. Jason Berman Berman’s laboratory where he and his research team conduct research using the zebrafish model to study hematopoiesis and oncogenesis. “Zebrafish are transparent multi-celled organisms that rapidly generate a large number of offspring. This allows us to observe and manipulate gene networks, developmental processes and the interactions of diseased cells with their host environment in a more rapid and cost-effective manner than in other model systems,” explained Dr. Berman. “Through this unique 8 BIOTECHNOLOGY FOCUS November 2013

propriate CDRD drug development projects stemming from its network of over 30 Canadian health research institutions and select international centres. The CDRD Atlantic Node is also expected to be expanded into other areas as CDRD partners with additional experts throughout the region. CDRD president and CEO Karimah Es Sabar commented that this partnership is the first step towards a panCanadian network of CDRD Research Nodes “One of CDRD’s primary objectives is to increase the R&D resources available to Canadian researchers to advance their early-stage health-related discoveries towards commercialization; and one of our strategies to achieve this is to add to our existing extensive small molecule and biologics drug development platform by investing in and/or leveraging other leading-edge facilities that are unique and complementary in nature. As such, this is just the first in what we anticipate will be a pan-Canadian network of CDRD Research Nodes,” she said.

partnership with CDRD, we will harness the tremendous power of the zebrafish model for the purpose of drug discovery, effectively pioneering these approaches in Canada for the first time.” Currently, Dr. Berman’s laboratory is located at the IWK, but in 2014 he will move his team into a new larger state-of-the-art facility in the Life Science Research Institute on Dalhousie’s campus. Through this Node, zebrafish models of disease, immunology To see this story online visit and oncology will be utilized to benefit ap- http://biotechnologyfocus.ca/?p=9307

BUSINESS CORNER Cardiome reaches commercialization agreement with Algorithm S.A.L. CardiomePharma Corp. subsidiary Cardiome International AG has entered into an agreement with Algorithm S.A.L to sell and distribute BRINAVESS™ (vernakalant intravenous) exclusively in certain Middle Eastern and North African countries. Under the terms of the agreement, Algorithm (which is headquartered in Beirut, Lebanon) has agreed to specific annual commercial goals for BRINAVESS. Financial details of the agreement have not been disclosed. The initial term of this commercial agreement begins November 1, 2013 for the duration of five years and is renewable on an annual basis. Countries covered by the agreement where Algorithm will be able to commercialize BRINAVESS include: Algeria; Bahrain; Egypt; Iran; Jordan; Kingdom of Saudi Arabia; Kuwait; Lebanon; Libya;

Morocco; Oman; Qatar; Tunisia; and United Arab Emirates. The deal is the second commercial agreement for the Vancouver-based company this month, having earlier signed an agree-

ment with Biospifar S.A., to sell and distribute BRINAVESS™ exclusively in Colombia. To see this story online visit http://biotechnologyfocus.ca/?p=9483

National Labour Market Information (LMI) study identifies biotech industry workforce trends

BioTalent Canada, along with Canada’s Research-Based Pharmaceutical Companies (Rx&D), has released a new Labour Market Information (LMI) report indicating that skills shortages and access to capital remain barriers to product development and business goals in Canada’s biotech industry. The report: Sequencing the data, People – Driving Canada’s Bio-economy, identifies key human resource (HR) challenges and trends for Canada’s biotech industry across all subsectors including life sciences and pharmaceuticals. With its partners, BioTalent Canada surveyed over 240 biotech companies to iden-

tify HR needs. As an effort to understand the importance of meeting the current and evolving needs of the industry, the LMI report shows how the industry continues to redefine itself and examines the human resources trends in Canada’s bio-economy, along with how they impact companies from all sub-sectors, sizes, and stages of growth, from all regions across Canada. Life Sciences Ontario (LSO), the Life Sciences Association of Manitoba (LSAM), PEI BioAlliance and Scotia Bank Start Right were supporting partners in preparing the report. The report shows companies continue to pursue paths to commercialization and indicates that having access to talent with the right skills is a critical factor in achieving success. Among the key labour market findings: • Capital: The single greatest challenge to product and service development is limited access to capital, which has increased from 65.9% to 73.8% between 2008 and 2013. • Skills Shortages: Skills shortages still remain an issue; 33.2% of companies report skills shortages among staff, which is in line with the 34.4% reported in 2008. Of those reporting skills short-

ages, 40% indicate it had a negative impact on their company. • Looking Ahead: Companies expect limited access to financial capital (19.83%) and a lack of practical/non-academic skills (16.53%) to be the biggest challenges in the next three to five years. “These challenges are opportunities for industry, government and academia to develop programs that will have a positive effect on the industry’s success, much like our Career Focus wage subsidy program has had,” said Rob Henderson, president of BioTalent Canada. “The industry and partner support from Rx&D, Life Sciences Ontario, Life Sciences Association of Manitoba, PEI BioAlliance and Scotia Bank Start Right for this study and report shows how important talent is to the industry’s success. We plan to work with our national and provincial partners to address these HR issues in the days ahead so the industry can focus on its real work – innovation, revenue and employment.” To view or download a copy of the full report, visit www.biotalent.ca/sequencing. To see this story online visit http://biotechnologyfocus.ca/?p=9204

November 2013 BIOTECHNOLOGY FOCUS 9

BUSINESS CORNER MedMira receives US army funding to expand use of diagnostic tests The US army is providing MedMira Inc. $1.917 million in additional funding for the development and commercialization of two rapid tests for transfusion transmitted diseases. The testing is being conducted under a United States Army Medical Research Acquisition Activity (USAMRAA) contract. The new financing will allow MedMira to conduct further tests for its Reveal Rapid Hepatitis B Surface Antigen Test and its Multiplo Rapid HBc/HIV/HCV Antibody Test in parallel with the current clinical trials. The company says it will use the clinical data acquired from the additional testing to obtain complementary label claims

and intended uses for the two rapid tests, which will in turn expand applications for both products. “The additional product testing that we can now perform on the Reveal and Multiplo products will allow our customers access to powerful diagnostic capabilities in a wider range of environments and situations,” said Kevin Jones, senior director, Global Sales and Marketing, MedMira. “The end result of the additional funding will be that more tests will be performed at a faster rate and a lower cost than has previously been attainable. The benefits for patients and healthcare providers using rapid tests built on our technol-

ogy platform, especially the Multiplo triple test, will be seen not just in the U.S., but by organizations across the globe.” MedMira hopes that the new testing will show that its Reveal and Multiplo products can be used beyond their original application for military healthcare in emergency medical situations and for screening transfusion transmitted diseases. The company aims to position the two products to be used in public healthcare initiatives such as disaster and humanitarian relief efforts. To see this story online visit http://biotechnologyfocus.ca/?p=9478

Feds announce two venture funds focused on the life sciences sector The federal government continues to roll out its Venture Capital Action Plan (VCAP) following the announcement by Canada’s Minister of Finance of a $50-million investment to help businesses access the capital they need through the creation of four venture funds. The CVCA Member fund recipients includes two funds focused on the life science sector. The two funds are the CTI Life Sciences Fund II and the Lumira Capital II fund. The government will be investing

in these funds on the basis of the recommendations made by an expert panel. In all, $15-million will go to the CTI Life Sciences Fund II and $10-million will go towards Lumira Capital II. The Business Development Bank of Canada will provide support and advice to the government as it implements the VCAP, by providing independent expertise, undertaking due diligence, supporting negotiations with funds and other investors, and assisting in the deployment of VCAP investments.

In addition to the $50 million investment, the announcement also included the launch of the Canada Accelerator and Incubator Program. The CAIP will go towards supporting Canadian start-up firms providing $60 million over five years to help incubator and accelerator organizations expand their services to worthy entrepreneurs. To see this story online visit http://biotechnologyfocus.ca/?p=9197

Dealmakers n The Centre de recherche sur les biotechnologies marines (CRBM) and Centre national de biologie expérimentale (CNBE) of Institut national de recherche scientifique (INRS) have signed a strategic partnership agreement to develop marine biotechnologies. The agreement provides CRBM with a research site where it can develop new products for its industrial partners, as well as greater access to projects on biological materials of marine origin. The CNBE, located on the INRS campus in Laval, QC, offers high standard preclinical research services to the scientific community and the biotechnology and pharmaceutical industries. Certified by the Canadian Council on Animal Care in Science (CCAC) and the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC International), it provides housing for laboratory animals at various levels of biological confinement as well as an array of services required by R&D projects. n Aeterna Zentaris Inc. (Québec City, QC) has completed its previously announced deal with Merck KGaA (Merck Serono) transferring the manufacturing rights for Cetrotide® to the Ger-

10 BIOTECHNOLOGY FOCUS November 2013

man based multinational. AeternaZentaris Inc. had previously monetized the royalty stream related to Cetrotide® in November 2008 in a transaction with HealthCare Royalty Partners L.P. (formerly Cowen Healthcare Royalty Partners L.P.). Under the terms of the agreement, AeternaZentaris will receive a one-time payment of approximately US$3.3 million. Cetrotide® (cetrorelix acetate for injection) is used to regulate hormone responses in women undergoing infertility treatment. Merck Serono currently markets Cetrotide® worldwide. n The Canadian Centre for Commercialization of Regenerative Medicine (CCRM) (Toronto, ON) and 360ip (Ngee Ann City, Singapore) have signed a collaboration agreement to work together in a variety of areas, including developing a fund to invest in best-in-class regenerative medicine (RM) technologies and companies in Asia, Europe and North America. The two sides made the announcement while attending Bio Japan 2013 in Yokohama, Japan. 360ip is a global technology commercialization, investment and fund management company, headquartered in Singapore, with teams

based throughout Asia and North America. Contract research organization JSS Medical Research (Montréal, QC) has acquired LatAm Clinical Trials, a multinational CRO in South and Central America. LatAm Clinical Trials was founded by a group of entrepreneurs in 2005 and has provided clinical research support to the pharmaceutical industry for Phases 1 to 4 clinical trials and post-marketing studies with offices in the USA, Colombia and Panama. The clinical research staff is located in the Andean Countries of South America and in Central America, giving access to substantial underutilized medical expertise and infrastructure throughout an area that includes Colombia, Panama, Costa Rica, Guatemala, Dominican Republic, Peru, Venezuela and Ecuador. LatAm Clinical Trials’ geographic reach is extended to additional countries in Latin America through partnerships with other local CROs in Mexico, Argentina, Brazil and Chile.

For more Business Corner news visit http://biotechnologyfocus.ca/category/ industryintel/

BUSINESS CORNER Roche Canada opens doors to new home On October 2, Hoffmann-La Roche Limited (Roche Canada) celebrated the grand opening of its new pharmaceutical headquarters in Mississauga, ON. The opening celebration was hosted by Ronnie Miller, president and CEO of Roche Canada, who was joined by Dr. Franz Humer, chairman of the Board of Directors of Roche Holding Ltd., colleagues from Roche Canada, as well as members of all levels of government, including the government of Switzerland. “This is a very exciting day for Roche Canada as we move into a building that is truly representative of our company and our future – bright, energetic and collaborative,” said Miller. Roche Canada’s pharmaceutical division, previously located at 2455 Meadowpine Blvd. in Mississauga, employs 621 people in Canada, 500 (full time, permanent) of whom are based in the head office in Mississauga. Employees will start moving into the newly renovated offices located at 7070 Mississauga Road immediately.

In conjunction with the opening, the Swiss international biotech giant Roche Holding AG also announced that through its Hoffman-LaRoche Limited unit, it will invest almost $200 million over the next five years at the Mississauga head office. The

INCUBATING INNOVATION AND INGENUITY

CSPC 2013 HIGHLIGHTS   

investment will be used to bring 200 highly skilled and specialized jobs to Canada’s life sciences sector. To see this story online visit http://biotechnologyfocus.ca/?p=9332

CONFERENCE HONORARY CO-CHAIRS The Honourable Michael H. Wilson Chairman Barclays Capital Canada Inc. Chancellor University of Toronto

600+ participants,150+ speakers, 28 panel sessions 3 Pre-Conference Workshops/Symposiums Inauguration of the Awards of Excellence in Science Policy - a first in Canada

Mandy Shapansky President and Chief Executive Officer Xerox Canada Ltd.

Early bird Deadline: October 20th, 2013

@sciencepolicy /canadiansciencepolicy Canadian Science Policy Conference

www.cspc2013.ca November 2013 BIOTECHNOLOGY FOCUS 11

By: Ian Rogers

REgENERATIvE MEDICINE

The importance of

umBiliCal Cord Blood Banking for present and future cell therapies

here are many reasons that umbilical cord blood (UCB) has become a major alternative donor source for blood and marrow transplantation. UCB can be collected from the umbilical cord and placenta after birth. The blood volume of about 80 to 100 ml contains approximately one billion blood cells consisting of one to ten million CD34+ stem and progenitor cells that can be used as donor cells for bone marrow transplantations. Moreover, stem cells found in UCB have the same properties as those isolated from the bone marrow but offer advantages that bone marrow cells do not. One main advantage is UCB is easily collected with little risk to the mother or baby. A second advantage is that the patient better tolerates a mismatched UCB unit as opposed to a mismatched bone marrow donor unit. Matching of the donor and the recipient is important for allogeneic transplants. Usually, a perfect match at eight or 10 HLA antigens is sought in order to reduce graft rejection and graft versus host disease. Finding a perfect match reduces the availability of a donor unit to those that have identical HLA antigens. Interestingly, the analysis of transplant data has revealed that a single-mismatched UCB unit (mismatched at one HLA antigen between the patient and donor) results in equal survival as a fully matched bone marrow unit. This translates into a larger available donor pool with UCB versus bone marrow because a perfect match is not required (NEJM 2007). The first single unit UCB transplant was conducted in 1988 using a sibling UCB unit. This first transplant, which took place in France, was successful and the patient from that procedure is still alive today. During the early years of UCB transplants, the therapy was limited to pediatric patients because the low number of cells in a typical UCB indicated that adult transplants would be risky. Currently, there have been over 30,000 transplants using UCB in children and adults. Improvements in matching and adult patient selection have also led to more successful adult transplants. Studies have since demonstrated that increased cell dose yields better outcomes. For many adult transplants, two UCB units are used and they can each be partially mismatched to each other and the patient and still yield positive outcomes. As transplant centres become more familiar with using UCB as a donor source and as innovations lead to an increase in adult UCB transplants, the demand for donors will increase.1

Public and Family Banks: Currently, public banks that are usually funded by local or federal levels of government are the ones to collect UCB. Public access banks will collect only at designated hospitals and keep a wide range of different HLA-types 12 BIOTECHNOLOGY FOCUS November 2013

REgENERATIvE MEDICINE What are UCB stem cells used for?

Bottom Left: A UCB collection bag. Bottom Right: Human UCB in a blood vessel in a mouse liver post transplantation. The blue are nuclei and the blue with the yellow-green dots around it is a human blood cell with the mitochondria labeled so it can be distinguished from the mouse cells. on hand. There is no fee for the collection or storage and the UCB unit’s HLA type is uploaded into an international registry so patients around the world have access to suitable units. When a unit is released to a transplant centre, the public bank levies a charge of $30,000 to $50,000. In Canada, for example, this fee is paid by provincial government medical plans, such as OHIP in Ontario. In the U.S., many health insurance companies cover these fees. One of the longest running public UCB banks is the National Cord Blood Program run by the New York Blood Center that collects at eight affiliated hospitals in the New York area, Virginia and Ohio.2,3 An alternative to the public bank system is private banks (also known as family banks), which are companies that charge a fee for the collection and storage of the UCB unit, which is then held for the family. Family banks such as Insception-Lifebanks in Canada4 and Cord Blood Registry in the U.S. were established in the mid 1990s. Until very recently there were only two public banks in Canada, one in Alberta that was funded by a provincial grant, and the second located in Québec, run by HemaQuébec. The Canadian national umbilical

cord blood bank started collecting units on September 30, 2013.5 In doing so it became the last of the G8 countries to start a national program for collecting and storing umbilical cord blood units for the general public. In Canada and the U.S., only about three to five per cent of all births will result in cord blood storage, either in private or public banks. Considering there are over three million births annually in these two countries, millions of units are currently being tossed away as biological waste. For non-caucasians, the chance of finding a match can be very low, so there is a need increase UCB banking, especially for ethnic Canadians. The establishment of a public bank will facilitate the storage of samples for use by Canadians, but it should also provide units for international patients, through international registries such as Euro Cord and Net Cord. The New York Blood Center has donated stored units to over 25 countries, including six transplant centres in Canada. With the establishment of a Canadian public bank, we will now not only be able to provide potential units for Canadian patients, but Canada will now be able to contribute to the world-wide pool of available units instead of just being an end user of UCB.

In the last five years there has been an increase in UCB use for bone marrow transplants in pediatric patients and more recently, in adults. The 2011 transplant data from the New York Blood Center shows that 62 per cent of the UCB units were used to treat leukemia and another 26 per cent were used to treat other blood-based diseases. Interestingly, six per cent were used to treat metabolic diseases such as Hurler’s disease or Tay Sachs disease. Although half of these units were used to treat pediatric patients, roughly 30 per cent were used on adults.3 The data from private banks shows a different profile of the diseases treated and highlights an interesting difference between public and private banks. For example, Insception-LifeBanks (a large Canadian bank) has released units that were used to treat blood-related diseases similar to those treated with units from public banks. In these cases as would be expected a sibling was usually the donor. But units were also released that were used by the donors themselves. In other words, the unit was used autologously. In these cases the patient’s own UCB unit is considered disease free because the treatment is for a non-blood-based disorder. Autologous UCB transplantation was part of the treatment regimen for retinoblastoma (eye cancer), Type 1 diabetes and Cerebral Palsy.6,7,8 In the retinoblastoma cases, aggressive treatments to eradicate the cancer can damage the immune system, so having a source of blood stem cells available allowed doctors to treat the eye cancer and correct any subsequent damage to the immune system by using the patient’s own UCB cells. Likewise, using UCB for the treatment of Type 1 diabetes and Cerebral Palsy is based on properties of UCB that enhance wound healing and can modulate the immune system. Mature cells in the UCB unit, not the stem cells, are known to secrete a variety of proteins called cytokines that are involved in controlling the body’s response to injury from external forces, such as oxygen depletion during birth leading to Cerebral Palsy, or from internal factors such as an autoimmune reaction that damages islet cells, resulting in Type 1 diabetes. Treatments for these diseases are still experimental and in the clinical trial phase, but indicate there may be a wider use for UCB in the future. Dr. Kurtzberg at Duke University has been conducting trials using a patient’s own UCB to treat Cerebral Palsy since 2010. The concept is that the neural damage causing Cerebral November 2013 BIOTECHNOLOGY FOCUS 13

Regenerative Medicine

Palsy can be reduced by the infusion of the patient’s own UCB blood, which then helps reduce inflammation of the brain tissue and increases blood flow to the damaged area, thus reducing the amount of neural damage. In the case of Type 1 diabetes, the hypothesis is that UCB will reduce the autoimmune initiated damage of the islets, thus slowing down the progression of the disease. In both Cerebral Palsy and Type 1 diabetes the UCB treatment does not eradicate the disease but is expected to slow down its progression. What these diverse treatments bring to light is that there are allogeneic (non-self) uses of UCB, which is the main use of the UCB units from public banks. It is logical that the treatment of blood cancers does not use the patient’s own UCB unit as it may contain cells that are cancerous. Therefore, a healthy UCB unit offers the best treatment. But in the case of a non-blood disorder, the patient’s own UCB unit would be healthy and present less risk for transplantation, which is why autologous UCB, stored in private banks, has been used for the Cerebral Palsy treatment study. The ability of UCB cells to enhance tissue healing has also been demonstrated in pre-clinical animal studies. For example, UCB has been shown to reduce late stage tissue damage in a model of spinal cord injury.9 Therefore, it is possible that in the future, UCB can be used to treat non-healing diabetic wounds, tissue ischemia, traumatic brain injury and spinal cord injury.

The future of UCB as a source of cells for cell based therapies: UCB is becoming a standard of care for the treatment of blood disorders and cancers. At some centres, it is already preferred over bone marrow stem cells as a donor source. The problem with collecting and storing such cells for transplant is the cost of doing so. The Canadian National Cord Blood Program run by the Canadian Blood Services was started with $35.5 million from the federal, provincial and territorial governments. Canadian Blood Services is tasked with raising another $12.5 million to ensure the costs of running the bank is covered.5 There are successful ex14 BIOTECHNOLOGY FOCUS November 2013

The Canadian National Cord Blood Program run by the Canadian Blood Services was started with $35.5 million from the Federal, Provincial and TerritorIAL governments. Canadian Blood Services is tasked with raising another $12.5 million to ensure the costs of running the bank is covered. amples of public banks in many other countries and in the U.S. there are multiple public banks but even with the fees collected from units sent for transplant, it is a costly endeavor that requires, and merits, the support of all levels of government and the public. Public banks in Canada will collect from a few locations, including Ottawa and Mississauga, ON, as well as in Edmonton, AB. Their goal is to amass a sufficiently diverse collection of units to cover everyone in Canada. It has been estimated that a diverse collection of 20,000 units, the budgeted goal of the Canadian Bank, should be sufficient. In theory this is the expectation, but even with over 10 million registered bone marrow donors, many people requiring a bone marrow transplant cannot find a suitable donor. With only three to five per cent of all UCB samples being collected and stored, the importance of increasing collections cannot be undermined. Public and private banks currently store over two million units worldwide, but this inventory needs to be increased.10 An interesting concept that may address the funding problems public banks face is a hybrid bank that has both a public and private arm. The private arm would help to generate the revenue that a public bank can’t generate on its own. One such bank, CORD:USE Cord Blood Bank was founded and run by four of the world’s leading transplant physicians and experts, who are all

avid public bank supporters. The CORD:USE private arm is aptly referred to as the family bank, since a unit stored by the paying family will be saved for use by the family, and its public bank arm will store units from the donor that will be accessible by all.

References: 1. Ballen, Blood, 2013 122: 491-498 2. National Marrow Donor Program: http:// bethematch.org 3. New York Blood Center: http://www. nationalcordbloodprogram.org/ 4. Insception-Life Bank: www.insception. com 5. One Match, Canadian National UCB program: www.blood.ca 6. www.clinicaltrials.gov 7. Cerebral Palsy: Bone Marrow Transplant. 2013 Jul;48(7):890-900. 8. Type 1 Diabetes: Pediatr Diabetes. 2013 Sep 19. doi: 10.1111/pedi.12072. [Epub ahead of print]. 9. Spinal Cord Injury: Spine (Phila Pa 1976). 2010 Jul 15;35(16):1520-6. 10. Parent’s Guide to Cord Blood Banking: http://parentsguidecordblood.org/ To see this story online visit http://biotechnologyfocus.ca/ the-importance-of-umbilicalcord-blood-banking-for-presentand-future-cell-therapies

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OPINION

New approaches to

manage

CanCer

are deSPeraTely needed There were an eSTimaTed 12.7 million new CaSeS of CanCer worldwide in 2008 (wiTh 7.6 million deaThS). The inCidenCe of CanCer iS eXPeCTed To inCreaSe To 21 million new CaSeS By 2030. deSPiTe TremendouS SCienTifiC advanCeS in ThiS field, There remainS a large unmeT mediCal need for new CanCer drugS wiTh SuPerior effiCaCy, imProved SafeTy ProfileS and enhanCed ConvenienCe for The PaTienT. Cancer drugs generated global sales revenues of $48 billion in 2008, representing about six per cent of the pharmaceutical market. The cancer drug market is growing at almost twice the rate of the pharmaceutical market with a CAGR of 12 to 15 per cent. This large market opportunity has attracted intense competition. Some estimate more than 9,000 cancer drugs are under evaluation worldwide. In the U.S. alone, more than 900 cancer drugs are in clinical development. However, the majority of these investigational drugs are directed towards a small number (an estimated 16 or so) of molecular targets. A commonly held belief characterizes cancer clinical trials with a low success rate. Yet, the likelihood of a successful NDA for a cancer drug entering clinical development still exceeds six out of 12 pharmaceutical categories and is rapidly improving. Cancer drugs entering clinical testing from 1999 to 2004 had a success rate of nearly 20 per cent as recently reported by Dr. DiMasi and colleagues at the Tufts Center for the Study of Drug Development (Clin. Pharmacol. Ther. 94: 329-335, 2013). Interestingly, compounds studied solely in hematological indications had an even higher success rate, and unlike other fields, small molecules had a higher success rate than large molecules. 16 BIOTECHNOLOGY FOCUS November 2013

By: Robert Foldes

Several factors contribute to the traditionally low success rate of cancer clinical trials. First of all, cancer is not a single disease and it is extremely heterogeneous both in its origins as well as its manifestation. This usually translates to a heterogeneous patient population enrolled in clinical trials, including a large number of patients that are not predisposed to respond to the investigational therapy. The cancer phenotype is characterized by a large number of contributing pathways creating redundancies and compensatory mechanisms. Targeting one pathway may sometimes lead to only a temporary response. Recurrence of the disease can also be attributed to the presence of cancer stem cells. Secondly, patients enrolling in cancer clinical trials are usually no longer responding to one or more established treatment regimens. Mechanisms contributing to such drug resistance usually apply in a more general sense and are not drugspecific. Trials with such refractory patient populations usually lead to marginal results. And finally, approaches to address the above issues involve considerable stratification of patient populations to identify those most likely to respond to the investigational drug. This reduces the eligible patient population considerably, and together with the intense competition for those patients, makes enrollment challenging. Nevertheless, there is no question that stratification of patient populations to identify those most likely to respond to, and benefit from the investigational therapy is an important approach that is increasingly possible with the identification of suitable molecular markers. Thus, by applying this approach to a patient population that is not heavily pre-treated or with end-stage disease, it becomes more likely to increase the success rate. One strategy that has caught my attention, and is central to the focus of Viteava Pharmaceuticals, is referred to as “cancer interception.” I believe the Nobel laureate, Elizabeth Blackburn, coined this term to refer to delaying or avoiding the progression of cancer in early-stage patients (see Cancer Prev. Res. 4: 787792, 2011). Not to be confused with cancer CONTINUED ON PAGE 25

By: Mélanie Bourassa Forcier and Julie Desrosiers

SPOTLIGHT

Canada and EU Comprehensive Economic and Trade Agreement (CETA) reached in principle: What is the impact on pharmaceutical patents?

also have the effect of delaying the entry of generic competition.

On October 18, 2013, after more than four years of negotiations, Canada and the European Union reached, in principle, a free trade agreement, the Comprehensive Economic and Trade Agreement (CETA). By reaching this agreement, Canada agrees to two important demands of the European Union concerning the intellectual property rights of Canadian innovative pharmaceutical companies, in order to bring its intellectual property system in line with other Western countries. These demands were (1) the adoption of a patent term restoration for pharmaceutical patents and (2) an effective right of appeal under the Patented Medicines (Notice of Compliance) Regulations.

It is also understood that Canada will provide innovative brand companies with an effective right of appeal under the Patented Medicines (Notice of Compliance) Regulations. This will require amendments to the Regulations and will reverse the jurisprudential trend in Canada to the effect that, when the prohibition application of the innovator is dismissed and the notice of compliance of the generic is subsequently issued as a result, any appeal by the innovator becomes automatically moot unless the Court exercises its discretion to nevertheless hear the appeal. (Pfizer Canada Inc. v. Apotex Inc. (2001),

1. Patent Term Restoration Although the text of the agreement has not yet been released, it is understood that Canada will implement an up to two-year patent term restoration in order to compensate for the administrative procedures (particularly related to the approval of new drug submissions) that take place between the filing of a patent application for a drug and the issuance of the first notice of compliance. This two-year patent term restoration may

2. Right of appeal under the Patented Medicines (Notice of Compliance) Regulations

11 C.P.R. (4th) 245, para. 21 (C.A.F.) (application for leave to appeal dismissed with costs, S.C.C. [2001] S.C.C.A. no. 111); Apotex Inc. v. Merck Frosst Canada Inc., [1999] J.C.F. 55, paras. 4-6 (C.A.F.). Finally, it is expected that the future amendments will address duplicative patent litigation sometimes generated by the Regulations. Members of the innovative pharmaceutical industry have welcomed the new agreement although some would also have hoped for an extended data protection period, increasing the current eight-year period of protection to a 10+1-year period of protection as currently provided by European countries. No full text of the agreement has been released yet. The ratification is expected to take 18 to 24 months. Mélanie Bourassa Forcier and Julie Desrosiers are members of the Fasken Martineau LLP Montréal office Life Sciences Group. Republished with permission ofthe Fasken Martineau LLP Montréal office Life Sciences Group To see this story online visit http://biotechnologyfocus.ca/ canada-and-eu-comprehensiveeconomic-and-trade-agreementceta-reached-in-principlewhat-is-the-impact-onpharmaceutical-patents November 2013 BIOTECHNOLOGY FOCUS 17

By Noel Courage

BIoSIMILarS

biosimilar

biosimilar biosimilar biosimilar patent enforCement in Canada

here is much interest in developing lower-cost biosimilar (subsequent entry) copies of biologic drugs, such as filgrastim and erythropoietin, for the Canadian market. Brand name companies that have spent huge amounts of time and money pioneering these biologic drugs are keen to hold onto their exclusive markets as long as possible. Canada has a specialized litigation option available to protect certain patented drugs on the market. The process may block a second-entry drug that is referencing a patent owner’s clinical trial data. This unique Canadian system is informally called the “NOC Regulations.”1 It requires

18 BIOTECHNOLOGY FOCUS November 2013

generic and biosimilar drug companies to establish freedom-to-operate (clearance) with respect to certain patents as a precondition to market authorization. This is in sharp contrast to conventional Canadian patent enforcement litigation that typically begins only after marketing authorization is granted. In comparison, the U.S. has created its own specialized and complex biosimilar litigation process, which is beyond the scope of this article. This article will review the NOC Regulations as well as conventional patent litigation options that apply in proceedings involving biosimilars.

Health Canada Opens the Door to Biosimilars A biosimilar is a complex drug, such as a protein drug, that can be approved for sale on the basis that it is chemically similar to an innovator biologic drug already on the market.2 This standard for market approval is less strict than bioequivalence, which applies to conventional generic pharmaceutical drugs. For instance, showing biosimilarity allows biosimilar manufacturers to rely largely on the innovator drug’s clinical data, thereby dramatically reducing the time and expense otherwise required to obtain market authorization. Health Canada approves drugs for marketing by issuing a marketing

BIoSIMILarS The Health Canada Patent Register In connection with the NOC Regulations, Health Canada maintains its own Patent Register, independent from the Canadian Intellectual Property Office, relating to medicines and their use. The Patent Register is somewhat analogous to the U.S. Orange Book for conventional pharmaceutical litigation. However, Health Canada does not have any involvement in examining or issuing patents. The sole purpose of the Register is to prevent patent infringement in certain circumstances. Only a company that applies for, or already has an NOC for an approved patented drug may be eligible to take advantage of this specialized process. While only certain types of patents qualify, Health Canada clearly stated that biologic patents are eligible for the Register.5 For instance, to be eligible for listing, a patent must claim either an approved: • medicinal ingredient; • formulation that contains the medicinal ingredient; • dosage form; or • use of the medicinal ingredient. The Patent Register also has strict, non-extendable time limits. For instance, a patent can be listed at one of two times: • A patent that is issued at the time of ﬁling an NDS (or supplementary NDS) must be listed at the time of filing the submission; or • A patent application that has a ﬁling date before the filing of the NDS (or supplementary NDS), must be listed within 30 days after the issuance of the patent.

on the Health Canada Patent Register. If there are no relevant patents on the Patent Register, then Health Canada will not have to hold up drug approval pending resolution of patent issues. The Patent Register provides significant benefits to a patent owner by keeping a competitor from entering the market. In contrast, prior to the creation of the Patent Register, the patent owner often had to use conventional patent litigation to chase a competitor for patent infringement after the medicine was already on the market. This created inefficiencies since interlocutory injunctions are difficult to obtain and it takes a long time to bring a patent infringement case to a trial. The brand name company would lose significant market share in the meantime. The pre-emptive NOC Proceeding is a faster and cheaper way to keep a competitor off the market than a patent infringement trial. The filing of the NOC Proceeding starts an automatic 24-month stay of NOC issuance to the biosimilar company (it is, in effect, like an injunction). The NOC may only be issued when the patent expires or the biosimilar company wins the NOC Proceeding. In contrast, as mentioned above, it is typically very difficult to obtain an interlocutory injunction against a competitor in Canada in a patent infringement lawsuit. A disadvantage of filing the NOC Proceeding is in the event that the generic or

Health Canada vets all requests to list patents on the Register. authorization, called a Notice of Compliance (NOC). An NOC is issued when a drug manufacturer’s new drug submission (NDS) is approved. OMNITROPE (somatropin; human growth hormone) is an example of a biosimilar that has been approved in Canada by relying on clinical data for Pfizer’s innovator somatropin product.3 Also, Health Canada recently published guidance on the regulatory pathway for biosimilar approval in Canada.4 Now that the regulatory pathway has been clearly laid out, innovation companies are reviewing and attempting to improve their patent barriers, while biosimilar manufacturers are trying to find a safe pathway for freedom-to-operate with respect to patented drugs in Canada.

Patent Register Procedure In order to receive marketing authorization, the biosimilar company must address freedom-to-operate with respect to patents

now that the reGulatory pathway has been Clearly laid out, innovation Companies are reviewinG and attemptinG to improve their patent barriers, while biosimilar manufaCturers are tryinG to find a safe pathway for freedom-to-operate with respeCt to patented druGs in Canada.

November 2013 BIOTECHNOLOGY FOCUS 19

BIoSIMILarS

Conclusion

in a Conventional patent infrinGement suit, the patent owner would typiCally sue for patent infrinGement and reQuest remedies suCh as damaGes or an aCCountinG of profits. aCCountinG of profits is a remedy that is an alternative to damaGes, in whiCh the plaintiff reCeives the defendant’s profits from the infrinGement.

infringed, valid and enforceable, and a court injunction was issued that would keep Amgen off the market until December 2013.

Conventional Patent Infringement Lawsuit

biosimilar company wins, the patent owner may be liable to the competitor for costs and damages for delaying biosimilar drug entry into the market. The NOC Regulations have been extensively litigated in the context of conventional, small molecule pharmaceuticals. Notwithstanding that an NOC Proceeding has not yet been completed for a biosimilar, the NOC Regulations will become an important patent protection tool as biosimilar development increases. The first biosimilar NOC Proceeding involved Teva’s biosimilar version of filgrastim.6 Amgen had the first approved filgrastim product in Canada, under the brand name NEUPOGEN, which expires on July 31, 2024. Amgen started an NOC Proceeding in an attempt to block Teva’s biosimilar filgrastim. In defence, Teva had alleged that claims of the Amgen patent in issue were either invalid, infringed or not relevant. The case was settled in August 2013. Amgen still has the only approved filgrastim product in Canada as of the time of writing this article. The terms of the Canadian settlement are unknown since neither company appears to have issued a press release on its terms. It is possible that the settlement may involve Teva keeping its filgrastim product off the market for a period of time. In the U.S. patent litigation on the filgrastim product (which is completely independent from the Canadian litigation), Teva had earlier admitted in a settlement that certain Amgen U.S. patent claims were 20 BIOTECHNOLOGY FOCUS November 2013

A conventional patent infringement lawsuit may be brought by a patent owner, irrespective of whether it has engaged in an NOC Proceeding. The patent owner can commence the patent infringement lawsuit in Federal Court, even if it lost in an NOC Proceeding. Likewise, the biosimilar company may lose in the NOC Proceeding, but later establish at a trial that the patent is invalid or not infringed. Additionally, Canadian patent infringement litigation is more extensive and permits discovery and trial testimony. In a conventional patent infringement suit, the patent owner would typically sue for patent infringement and request remedies such as damages or an accounting of profits. Accounting of profits is a remedy that is an alternative to damages, in which the plaintiff receives the defendant’s profits from the infringement. An injunction and delivery up to the patent owner of the infringing drug may also be requested. An injunction may also be requested before trial, but is unlikely to be granted because it is very difficult for a patent owner to show irreparable harm not compensable by damages, which is a precondition for the interlocutory injunction. In infringement proceedings, the biosimilar company may challenge the validity of a patent, for example, that the patent claims lack novelty, inventiveness or support. A patent is presumed valid during litigation and the onus is on the challenger to invalidate a patent. Also, while evidence used to attack validity of a patent in another country may be useful in Canada, each country has different laws and standards on patent validity issues. It would typically take at least a couple of years (often much longer) before a trial decision.

Patent owners and biosimilar manufacturers need to be prepared to engage the unique Canadian NOC Regulations. The protection for patent owners is a helpful supplement to conventional patent infringement litigation. Indeed, there is no down side to listing on the Register. If Health Canada accepts the list for its Patent Register, the ball is then in the biosimilar manufacturer’s court to address non-infringement and validity issues before receiving an NOC. As such, biosimilar manufacturers may have to prepare for a delay in market access regardless of the merits of the patent owner’s case; where there is a patent on the Register, the patent owner ultimately controls whether the parties go to court and the statutory stay in marketing authorization during the NOC Proceeding is automatic. These factors raise significant barriers to freedom to operate in Canada.

References 1. Patented Medicines (Notice of Compliance) Regulations, SOR 93-133. 2. For a review of biosimilar drug regulations, see: Noel Courage and Ainslie Parsons. The Comparability Conundrum: Biosimilars in the United States, Europe and Canada, (2011) 66 Food and Drug Law Journal, pages 203-224. 3. Health Canada, Health Products and Food Branch, Summary Basis of Decision (SBD) PrOmnitropeTM (Sep. 14, 2009), “Omnitrope Health Canada Approval”. 4. Health Canada, Health Products and Food Branch, Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biology (SEBs), Mar. 5, 2010. 5. Health Canada Guidance Document, Patented Medicines (Notice of Compliance) Regulations (March 8, 2010), at page 8. 6. Amgen Canada Inc. et al. v. Teva Pharmaceutical Industries Ltd. et al. (T-989-12).

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Noel Courage is a partner and patent agent with Bereskin & Parr LLP, Toronto, Canada. Noel can be reached at 416-957-1655 (ncourage@ bereskinparr.com)

To see this story online visit http://biotechnologyfocus.ca/ biosimilar-patent-enforcementin-canada

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By Shawn Lawrence

Innovator

Getting Cancer at the root of

One of the more interesting Canadian biotech stories of the 2013 calendar year took place back in April, when two Toronto-based companies, Stem Cell Therapeutics Corp. (SCT) and Trillium Therapeutics Inc. (Trillium), came together in a reverse merger transaction.

t was interesting in the sense that the company undertaking the reverse takeover, Trillium, acquired all the assets of Stem Cell Therapeutics including its name. The real value of the deal however according to the man heading up this new entity as president and CEO, Dr. Niclas Stiernholm, is that it gave Trillium access to the public markets. “As Trillium, we were a private company that had survived for nearly a decade on venture capital investment and when that well dried up, we relied heavily on our licensing revenues,” says Stiernholm who for more than ten years was CEO of Trillium. No stranger to big transactions, one of the more famous licensing transactions involving Stiernholm and Trillium was with Genentech in 2004. “That was big news, and represented our first real accomplishment. It put us on the map, in newspapers and on television. We worked with Genentech for about four years and over the life of the agreement generated between five and six million dollars in licensing revenues. We established similar deals with other companies. In a way it brought some validation to our science and we learned a lot from these 22 BIOTECHNOLOGY FOCUS November 2013

partnerships and how to develop products successfully. The downside of course was that we sold off some of our most precious assets because we were always in survival mode.” With a dwindling cash balance and increasing pressure from his investors, Stiernholm was left with two options to seek out new capital, one of which was to sell off another precious asset. Fortunately, that’s when SCT approached him about the possibility of the merger. “SCT had essentially two things to offer. Firstly, they had a public listing on the TSX venture exchange, which would provide access to public fundraising. Secondly, they had a positive cash balance. They had no staff, a pipeline that was virtually nonexistent, a part-time executive chair and no facility as they had closed down everything in Calgary, AB. It wasn’t so much an asset transaction as a financial one.” Some would call it an innovative solution to a problem that Canadian private biotech companies often face when considering the decision to go the Initial Public Offering (IPO) route. Specifically that the IPO route offers little certainty thanks to a volatile market with a shortage of available capital. “The merger was as such the best alterna-

innovator tive.” says Stiernholm. So Trillium punched its ticket onto the public market with the deal and was provided the cash it needed to get by. The only thing that was sacrificed in the deal was the company name. This was a small price to pay for creating a larger company with a better chance to advance its early-stage products. “The fact is, the company is still Trillium just with a different name and a different board of directors. We’re still in the same building with the same management and the same staff. And best of all, we didn’t have to sell our best product to get the deal done. This is important because I believe it’s necessary to keep your products in order to create value in a company.” Remarkably, it’s not the first time the company has changed its name. Trillium Therapeutics was actually established in 1996 under the name Transplantation Technologies Inc. Back then it was a spin-out company from six academic institutions in Ontario. Its focus, as the name implies, was transplantation - specifically xenotransplantation, which involves transferring organs from genetically modified animals such as pigs to humans. “Transplantation Technologies remained largely an academic exercise. It was mostly grant driven, with no real money or venture funding. The company stayed afloat, but the technology didn’t succeed. By the time 2002 rolled around, they had branched out to become more of a general immunology company, and that’s roughly the time I came on board,” says Stiernholm. To this day the company’s focus continues to be on finding ways to manipulate the patient’s immune system to treat disease. Specifically, they are focusing on using immunotherapy to block negative pathways in malignant cells, including cancer stem cells. One such immunotherapy is the company’s lead product, SIRPαFc, the same product that Stiernholm was reluctant to sell believing it would inevitably drive value in the company. “SIRPαFc blocks CD47, an extremely interesting and attractive target that is expressed not only on bulk cancer cells but also on cancer stem cells. CD47 is like a stop sign – it tells the immune system not to attack. Cancer cells overproduce this protein and use it to protect themselves from immunemediated destruction. Our drug binds CD47 and prevents it from delivering this suppressive signal, enabling the immune system to kill the tumour cells,” he explains. The development of the SIRPαFc fusion protein originated from leading researchers

“I think we have some very interesting data showing that we are indeed blocking the CD47 stop signal and activating the immune system to do what it is capable of doing – killing tumour cells.” in the field, including Drs. John Dick and Jean Wang of the University Health Network, and Dr. Jayne Danska of the Hospital for Sick Children, all of Toronto. SIRPαFc is being developed initially as a treatment for acute myeloid leukemia (AML), and has recently entered formal IND-enabling studies. “I think we have some very interesting data showing that we are indeed blocking the CD47 stop signal and activating the immune system to do what it is capable of doing – killing tumour cells.” According to Stiernholm, another exciting finding thus far is that it appears that blocking CD47 can be used in combination with several of the best-selling approved cancer antibodies. “These are billion dollar products and it appears that our approach will augment their activity, providing the opportunity for combination therapy and a strong synergyyet another positive feature of this program. We really think this is going to be the next big thing in immunotherapy and we see many potential pharmaceutical partners sharing that view,” he says. The second product in the pipeline is also a cancer stem cell therapy. The tigecycline program was optioned from the University

Health Network shortly after the merger. It is based on the work of Dr. Aaron Schimmer who discovered that tigecycline, an approved antibiotic sold by Pfizer, had strong anti-leukemic activity both on bulk cancer cells and cancer stem cells. Prior to the option agreement, it had already entered into a Phase 1 clinical trial in AML patients at four sites in North America. “Dr. Schimmer’s research is focused on drug repurposing – finding new indications for approved therapeutics. Focusing on established drugs with known safety profiles can significantly lower the risk in the drug development process, saving time and costs.” For this discovery, Dr. Schimmer received the 2012 Till McCulluch Prize and in 2013 won an award from the Canadian Cancer Society. “We are really excited by this program and pleased to be working with Dr. Schimmer. He is a young, up-and-coming clinician-scientist and these awards validate the significance of his work.” Stiernholm adds that this product demonstrates that SCT is more than just an immunotherapy company, because this product targets cancer’s metabolic pathways instead. “It’s very different from immunotherapy, yet it is still complementary to what we do. It’s another way of getting at the tumour. Both tigecycline and SIRPαFc target the cancer stem cell. We think of cancer like a weed, with cancer stem cells forming the root. To kill a weed in the garden you need to remove the root. Likewise, to cure cancer you need to destroy the cancer stem cell ‘root’.” The last product in the company’s preNovember 2013 BIOTECHNOLOGY FOCUS 23

Innovator “the reason i Came to toronto in the first plaCe was its reputation as an immunoloGy leader. i truly believe that in order for a small Company like ours to survive, it is essential to have a Good stronG relationship with aCademiC institutions and researChers.”

clinical cancer immunotherapy pipeline is its fully human CD200-specific monoclonal antibody. “The CD200 antibody is one of the foundational programs of Trillium. Recently we regained control of it when our partner was acquired by a third party. We don’t have the resources now to advance this program, so we are taking a wait and see approach.” In addition to its preclinical portfolio, Stem Cell Therapeutics is also conducting a clinical trial with TTI-1612 in patients with interstitial cystitis, a chronic and painful bladder disease affecting a great many people, especially women. “TTI-1612 is another Trillium legacy program which is outside of our core interests in immunotherapy and oncology. Nevertheless, it addresses a huge unmet medical need and a great market opportunity. Our strategy is to find a partner to advance this program,” he says. On the topic of the company’s core strategy going forward, Stiernholm’s aspirations are to strengthen the company’s position as a global contender in the cancer stem cell field. This includes capitalizing on Canada’s world class cancer stem cell discoveries and building on the company’s existing links with Ontario’s leading cancer research organizations. 24 BIOTECHNOLOGY FOCUS November 2013

“We want to fill that niche by being a much needed commercial vehicle for Canada’s world class cancer stem cell discoveries. Toronto has a rich legacy of stem cell research, and there is a definite need for commercial receptors for the great discoveries that continue to emerge.” He adds that immunology research is also strong in Toronto’s biomedical community, particularly at the University of Toronto, and there is a huge need for a receptor for their technologies. “The reason I came to Toronto in the first place was its reputation as an immunology leader. I truly believe that in order for a small company like ours to survive, it is essential to have a good strong relationship with academic institutions and researchers. One should never underestimate the importance of a supportive ecosystem. For us, the resources in Toronto, whether in immunology, stem cell research or oncology, are our lifeblood.” Dr. Stiernholm is also not afraid to look elsewhere for opportunities. One example of an outside relationship that has been cultivated by SCT was its recent deal with an internationally renowned prostate cancer research group in the U.K. In this instance, SCT took an option on worldwide rights to

a series of prostate cancer stem cell assets from the University of York. The assets originate from research funded by Yorkshire Cancer Research (YCR) and conducted in the YCR Cancer Research Unit, University of York, under the direction of professor Norman Maitland. “This is a whole new area for us because we’re focused largely on leukemia and hematological malignancies. The way we structured the arrangement was that we took an exclusive option to license this technology/ intellectual property for a limited time. During this period we can do some preliminary work in our lab and make sure that we’re comfortable with the technology and that it behaves in our hands the same as it has in the inventor’s hands. That’s not a bad model, as too often people jump into big licenses and then find out that perhaps it wasn’t exactly what they thought they were getting. So far, it’s turned out to be a very interesting program. We’ll just have to see where it takes us next.” To see this story online visit http://biotechnologyfocus.ca/ getting-at-the-root-of-cancer

Opinion continued from page 16 based on improved time-to-progression (TTP) or response rate (RR). The cancer field still requires knowledge of surrogate biomarkers that are predictive of disease progression. This would allow tarpharmaceutical interventions to mannew card:Layout 1 1/31/2013 geting 9:09 AM Page 1 age the surrogate biomarkers as previously accomplished with great success in other fields, such as in heart disease. The advent of drugs to suppress cholesterol synthesis, modify platelet aggregation or lower blood pressure has had a huge impact on clinical outcomes through an “interception” strategy. The cancer field is in some ways many years

Not to be confused with cancer chemoprevention or vaccines targeting generally healthy populations, cancer interception focuses on patients with an elevated risk of developing malignant cancer. chemoprevention or vaccines targeting generally healthy populations, cancer interception focuses on patients with an elevated risk of developing malignant cancer. In most cases, pharmaceutical interventions do not exist for these patients. Moreover, existing drugs that have been approved for cancer indications have mostly failed to migrate towards the treatment of these early-stage patients, or are suboptimal, due to issues relating to efficacy, safety, and/or convenience. There’s also the risk of introducing early resistance, jeopardizing the potential for drug response if and when the disease progresses. In many ways, early stage cancer patients are ideal for pharmaceutical intervention, while innovative drugs and clinical trials targeting this population are as of yet, limited. Of course, the regulatory landscape is of critical importance to cancer drug development strategies. Traditional approval endpoints such as overall survival (OS) would render cancer interception strategies very difficult to pursue. A recent review by Michael Shea and colleagues (Clin. Cancer Res. 19: 3722-3731, 2013) revealed that 64 per cent of regular oncology drug approvals between 2002 and 2012 were approved on the basis of endpoints other than OS. Of relevance to cancer interception strategies, the FDA has previously approved cancer drugs

behind the cardiovascular field in its approach to disease management. However, the gap is starting to close. Robert Foldes is president & CEO of Viteava Pharmaceuticals Inc. (www.viteava.com) and is a Principal Consultant at Cognovie Inc.

To see this story online visit http://biotechnologyfocus.ca/ new-approaches-to-managecancer-are-desperately-needed

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NEW PRODUCTS Pump KD Scientific’s new Allegro Peristaltic Pump System allows maintenance

manipulation of plates and specimens inside the working chamber. Chamber atmosphere circulates through a condensate controller and then a catalyst which removes any trace amounts of oxygen. Specifically designed for use by smaller laboratories, it could also be economical for larger labs.

Web: www.shellab.com free, continuous flow pumping for various fluids. The new pumping system can easily dispense in forward or reverse direction using its touch screen display. Additionally, all parameters are clearly displayed on the touch screen for easy viewing. The unit can be configured for a specific flow profile using the programmable multi-step operations available right on the pump. The Allegro System is available in three models: Allegro I uses a single channel pump head with flow rates up to 1500 ml/min; Allegro II uses a two channel pump head offering two individual flows or one combined flow up to 720 ml/min; Allegro III uses two single channel pump heads offering two individual flows or one combined flow up to 2,000 ml/min.

Web: www.kdscientific.com HPLC columns JM Science introduces a complete new line of Shiseido HPLC Columns. The CAPCELL PAK is an epochmaking HPLC column that integrates the separation performance of silica-based, polymer-coated packing material. CAPCELL PAK essentially provides columns of reversed phase partition mode, normal phase partition mode, and ion exchange mode.

Balances Mettler-Toledo has introduced a new line of analytical balances. The new balances ensure a high level of process security, enhance reproducibility of weighing results and facilitate compliance with industry regulations. New technological advances, such as the StatusLight indicator, also allows users to confirm the calibration and routine testing status of balances. In addition, the StaticDetect sensor technology ensures that weighing results are not influenced by electrostatic charge, thereby guaranteeing the accuracy and reliability of weighing results and improving laboratory operational efficiency. Web: www.mt.com Vapour pressure tester AMETEK

26 BIOTECHNOLOGY FOCUS November 2013

Web: www.petrolab.com Sterilizer The SteriMax Smart sterilizer from WLD-TEC is ideal for all laboratories, anaerobic environments and safety cabinets.It uses specifically focused infrared light which generates an IR hotspot for sterilizing inoculating loops at a temperature of 650° to 1100°C in only 5 to 10 seconds immediately and without any preheating. The sterilizer also has adjustable sterilization and cool-down timers for two users by front panel operation, and annealing tube made of special quartz glass or optional wear-resistant ceramics. Web: www.WLD-TEC.com

Petrolab Company, the distributor for Grabner Instruments, introduces Grabner’s new automatic tester for low-volatility measurements. Grabner developed the

Kit EMD Millipore introduces its CpGenome™ Direct Prep Bisulfite Modification Kit. This kit performs bisulfite conversion directly from cells, tissues, blood and formalin fixed paraffin embedded (FFPE) samples without DNA purification. By eliminating the need to isolate genomic DNA prior to performing bisulfite analysis, the kit provides a simple and reliable protocol for one-step bisulfite conversion. The new kit offers conversion efficiencies of more than 99.5% and only requires limited amounts of input material, working with as few as 10 cells or as low as 50 pg of DNA. It is suitable for downstream analysis by methylation specific PCR, restriction digestion, sequencing and microarray hybridization, and its in-column desulfonation allows for the recovery of DNA without additional precipitation steps, producing more consistent results.

MINIVAP VPXpert-L to automate the manual ASTM D2879 Standard Test Method for Vapor Pressure by Isoteniscope. The analyzer measures gasoline, jet fuels, solvents and chemicals as well as food, flavor and fragrance products with vastly improved precision. The analyzer is optimized for a pressure range from 0.1 to 100 kPa and shows a measuring repeatability better than 0.1 kPa. The instrument requires only 1 mL of sample per test, eliminates the

Web: www.millipore.com/catalogue/ item/17-10451

Web: www.jmscience.com Anaerobic chamber Sheldon Manufacturing’s BactronEZ is an ideal first anaerobic chamber or replacement chamber for users looking to upgrade their existing chamber. The BactronEZ has a 13.7 cu.ft. workspace and a 300 plate capacity incubator. Bactron systems have airtight construction of stainless steel and rigid Plexiglas for unobstructed vision and integrity. The patented cuffs form a comfortable seal around the operator’s arms, permitting bare hand

need for vacuum pump and manual filling, and yields results within minutes.

NEW PRODUCTS Fume hood Air Science has introduced its new Purair ECO™ line of Energy-Saving Ductless Fume Hoods. The hoods are designed for both chemical and particulate protection for a wide range of laboratory and industrial applications. The Purair ECO is available with a choice of controllers including the company’s new ECOair™ touchpad control with color display interface. An optional BACnet network interface connects all cabinet control, monitoring and alarm functions to an open-source facility monitoring system. The system is based on an industry-wide, non-proprietary ASHRAE compliant protocol for green building management.Purair ECO is available in five standard sizes from 30” wide to 69” wide.

Media dishes Sartorius Stedim Biotech (SSB) introduces Microsart @media to

monochromator and filter technology for reading technologies including UV/VIS Absorbance, Fluorescence and FRET, and BRET and BRET². The company’s patentpending optical concept ONE-4-ALL is employed for sensitive luminescence, fluorescence and absorbance measurements – with performances as in dedicated instruments – in the Mithras² for filterbased reading. Additionally the instrument is equipped with two double monochromators with high blocking efficiency and f-number (increased transmission) for filter-less measurements of absorbance and fluorescence. For sensitivity in luminescence, a third specially selected and noise-reduced detector is engaged in the HiSens position which is used for Alpha and BRET readings as well.

Web: www.Berthold.com/bio

Web:www.airscience.com Pipettes Denville Scientific Inc. has launched its Ultra EZpetteTM Ultra High Precision Digital Pipettors. The new Ultra EZpetteTM provides both accurate and precise liquid dispensing in a comfortable ergonomic design. The pipettes are available in the choice of pink or blue with eight different models that cover volume ranges from 0.1µL to 10mL. The ejector has a unique “clik-to-fix” system to easily adjust the tip ejection. The Ultra EZpetteTM also includes a calibration tool for easy in-lab recalibration.

complement Microsart @vance, a product line for microbiological quality control in these sectors.Microsart @media are agar media dishes for Microbial Limits Testing. They are pre-filled with various agar media types, such as Tryptic Soy Agar or R2A Agar, sterile packaged and ready-touse in combination with Microsart @filter units. The new media dishes feature an innovative patented lid that allows touchfree transfer of the filter membrane onto the media without using any tweezers. This liftable lid gives easy access to the colonies after incubation. The touch-free membrane transfer eliminates membrane manipulation and handling, thereby minimizing a major source of secondary contamination.

Liquid handling The PDS-100 from Fluid Metering Inc. is a new solution for high precision, micro-volume production dispensing of fluids used in the manufacturing and assembly of medical catheters, stents, & blood tubes. The PDS-100 is a programmable fluid metering and dispens-

Web: www.sartorius.com Microplate reader Berthold Technologies introduces the second generation of its Multimode Microplate Reader Mithras. The Mithras2 LB943 comes with ing system which uses Fluid Metering’s patented CeramPump® valveless pump technology with precision, programmable drive motor control. The pump head internals are made from chemically resistant, sapphire-hard ceramics, ideal for dispensing a broad range of fluids. The PDS-100 is available in both single and dual pump head configurations. The PDS-100 can dispense from 3 uL per dispense up to 2 L/ min continuous flow at 1 per cent precision or better.

Web: www.fmipump.com

Web: www.denvillescientific.com November 2013 BIOTECHNOLOGY FOCUS 27

CALENDAR November 2013 November 13-14 12th Annual Market Access Summit, Canada Venue: Toronto, ON Tel: 1-866-298-9343 Fax: 1-866-298-9344 Email: customercare@strategyinstitute.com Web: www.marketaccesscanada.ca

2013 MRS Fall Meeting & Exhibit Venue: Boston, MA Tel: 724-779-3003 Fax: 724-779-8313 Email: info@mrs.org Web: www.mrs.org

December 2-4

Therapeutic Area Partnerships Venue: The Hyatt Regency- Boston, MA Tel: 949-797-7147 Cell: 949-413-0072

10th Annual Canadian Renewable Fuels Summit Venue: Montréal, QC Tel: 613-594-5528 Email: a.kent@greenfuels.org Web: www.greenfuels.org/en/industryinformation/summit.aspx

November 20-22

December 7-10

Canadian Science Policy Conference (CSPC) Venue: Toronto, ON Email: lauren.ashton@sciencepolicy.ca Web: www.cspc2013.ca

2013 ASH Annual Meeting and Exposition Venue: New Orleans, Louisiana Web: http://www.hematology.org/Meetings/ Annual-Meeting/

November 26

December 11

Global Health Conference Venue: Toronto, ON Tel: 519-661-2111 Email: healthinnovation@ivey.ca Web: http://sites.ivey.ca/healthinnovation/

LSO Annual Fall Symposium: Catalyzing Collisions & Clusters Venue: Mississauga, ON Tel: 416-426-7293 Email: admin@lifesciencesontario.ca Web: www.lifesciencesontario.ca

November 18-20

DECEMBER 2013

December 11-12

December 1-6

FDA/CMS Summit

Venue: Washington, DC Tel: 949-797-7147 Cell: 949-413-0072

January 2014 January 6-11 Venue: Amelia Island, FL Email: wc2014@chem.usmass.edu Web: http://icpinformation.org

January 18-22 SLAS 2014 Venue: San Diego, California, United States Web: http://www.biotech.ca/en/ what- we-do/2013events.aspx

January 30 Biotransfer Venue: Toronto, ON Tel: 514-285-1922 Email: biotransfer@cnrc-nrc.gc.ca Web: www.biotransfer2014.ca

June 2014 June 23-26 Bio International Convention Venue: San Diego, CA Tel: (202) 962-6655 Web: convention.bio.org

Company & Advertiser Index COMPANY Page Website AeternaZentaris........................................................................................... 10 .......................................................................................www.aezsinc.com Albert at Bay.......................................................................................................31..................................................................................... www.albertatbay.com Angiochem................................................................................................... 6...................................................................................www.angiochem.com Best Western Victoria Park Suites...................................................................31....................................................................................www.victoriapark.com Cardiome...................................................................................................... 9......................................................................................www.cardiome.com City of Mississauga ............................................................................................2............................................................................. www.winthehumanrace.ca CSPC 2013............................................................................................................11............................................................................................. www.cspc2013.ca EMD Millipore............................................................................................... 26..................................................................................... www.millipore.com Eppendorf...........................................................................................................32.......................................................................................... www.eppendorf.ca JM Science................................................................................................... 26....................................................................................www.jmscience.com JSS Medical Research................................................................................... 10..................................................................................www.jssresearch.com KD Scientific................................................................................................. 26................................................................................. www.kdscientific.com Mandel.................................................................................................................15................................................................................................ www.mandel.ca MedMira....................................................................................................... 10..................................................................................... www.medmira.com Merck KGaA.................................................................................................. 10................................................................................www.merckgroup.com Mettler Toledo............................................................................................. 26..............................................................................www.mt.com/liquidator Mimetogen Pharmaceuticals ....................................................................... 6..................................................................................www.mimetogen.com OBIO.......................................................................................................................7.......................................................................................................www.obio.ca POI Business Interiors.......................................................................................29........................................................................................................ www.poi.ca Roche Canada.............................................................................................. 11............................................................................... www.rochecanada.com World Stem Cell Summit 2013...........................................................................5...................................................................www.worldstemcellsummit.com 28 BIOTECHNOLOGY FOCUS November 2013

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THE LAST WORD

By Michael H. May

Taking the Pulse –

Indicators of Strength and Growth in the RM Industry I am often asked whether Regenerative Medicine has truly emerged as a viable industry. It has been almost 30 years since the launch of the industry’s pioneering companies. Are we there yet? I thought we were there in 2000 when Time Magazine issued the prophecy that “Tissue Engineer” would be the career of the future. Unfortunately, the hype generated by the financing of those pioneering companies and the promise Michael H. May, of engineered organs (e.g., “heart in President & CEO, a box”) would soon be corrected by a Centre for sharp decline in the industry, punctuated Commercialization by the bankruptcies of those pioneering of Regenerative companies and ethical/political debates Medicine (CCRM) surrounding the “savior” of this emerging industry – the embryonic stem cell. That correction has led to the (re)emergence of what we now refer to as Regenerative Medicine (RM). Today there are thousands of cell therapy trials underway globally. And what happened to those pioneering therapeutics companies? They now sell products focusing less on science than on manufacturing, distribution and quality systems. Of course, science still underlies the industry, advancing at an incredible pace and earning the sector a Nobel Prize last year. There are, however, several non-scientific indicators that commercializing RM in North America is approaching a “tipping point.”

More Funding is Being Directed to Translation The California Institute for Regenerative Medicine (CIRM) has transitioned in recent years from funding basic R&D and infrastructure to funding “disease teams,” which have strict timelines for achieving IND status around lead clinical applications. In addition, CIRM is proposing so-called Alpha-Clinics to educate the public on the state of stem cell therapies, deliver approved stem cell therapies to patients, and enable clinical trials of experimental treatments. One of the core areas of focus for my organization, the Centre for Commercialization of Regenerative Medicine (CCRM), is on technologies and processes that enable cell manufacturing. If even a fraction of the therapies currently in human trials are successful, there will be significant bottlenecks in scaling to commercial levels.

Industry Organizations and Consortia are Growing The Washington-based Alliance for Regenerative Medicine (ARM) has grown to over 150 member organizations. ARM promotes the industry to government, hosts several key annual events and leads standing committees that address industry-wide issues, such as regulation. CCRM has built a consortium of 30 plus companies from all sectors of the industry that co-invest in technology development, 30 BIOTECHNOLOGY FOCUS November 2013

provide market input in support of due diligence and stand as ready receptors for technologies emerging from CCRM’s development pipeline.

Deal-Making is Increasing Cephalon’s investment in Mesoblast helped create the world’s largest RM cell therapy company. During the past year, several large pharma and device companies made acquisitions, investments or closed licensing deals, which enhanced the flow of capital within the sector. ARM’s 2013 Annual Report stated that the total investment in RM companies in 2012 exceeded $1.2 billion, with 75 per cent of this investment coming in the form of equity investment. According to Toronto’s Lumira Capital Life Sciences, more money was raised in the biotech industry in the first half of this year through IPO than in any year since 2007. The recent IPO of RM industry leader Cellular Dynamics and Fate Therapeutics’ filing for IPO indicate that RM companies are participating actively in the current flurry of biotech investing. Canadian partners in CCRM’s industry consortium continue to progress. Toronto-based Tissue Regeneration Therapeutics (TRT) closed a multi-million dollar raise during the summer, Stem Cell Therapeutics merged with Trillium Therapeutics in April 2013 and STEMCELL Technologies continues to grow its reagent business globally. ARM’s Annual Report included an unweighted stock performance index of 29 RM companies with market caps greater than $10 million. Comparisons against the S&P500 and NASDAQ Biotech indices indicate that RM companies trended well against other biotech companies from March 2012 to March 2013. If there is any doubt that RM is attracting investor interest, the First Regen Med Investor Day, organized by ARM in NYC, attracted over 300 investors – double what was expected.

The Industry Gets its First Stem Cell Therapy Approval Health Canada approved Osiris’ Prochymal, in 2012, for acuteGvHD in children unresponsive to steroids. While approximately 12 cellbased products have been approved in regulated countries since 2008, this represented the first approval of a stem cell-based therapy. Earlier this year, CCRM and other stakeholders led a series of workshops to address the lack of consensus and standards associated with mesenchymal stromal cell (MSC)-based products. In September, a second workshop, led by CIRM, looked at the regulation of cell-based therapies in Europe, the U.S., Canada and Japan. I believe that close ties to the leading activities in the sector will create the right environment for bundling and launching the next wave of therapies and new companies in RM over the next five to 10 years. Certainly, the industry doesn’t want to wait another 30 years to realize returns on the current explosion of discoveries in the field.

Got something to say? Please send your comments/letters to biotechnology_focus@promotive.net

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Full page journal ad Biotechnology Focus - BFO

3/18/13 10:41 AM

Biotechnology Focus November 2013

Articles inside

THE IMPORTANCE OF UMBILICAL CORD BLOOD BANKING

BIOSIMILAR PATENT ENFORCEMENT IN CANADA

INNOVATOR

THE LAST WORD

OPINION