Biotechnology Focus April 2011 by Promotive Communications

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

DECEMBER 2011/ JANUARY 2012 VOLUME 15, NUMBER 1

CAN CANADA CLEAN UP IN

CLEAN-TECH? INSIDE:

STEREOTACTIC BODY RADIATION THERAPY IN EARLY STAGE NON-SMALL CELL LUNG CANCER Publication Mail Registration Number: 40052410

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contents DECEMBER 2011 / JANUARY 2012 – VOLUME 15 – NUMBER 1

The culmination of several important technological developments in radiation therapy

FEATURES STEREOTACTIC BODY RADIATION THERAPY A new method for delivering ablative doses of radiation safely in patients with early stage non-small cell lung cancer (By John Cho and Louis Lao)

14 Report on Canadian clean-tech says national industry is punching above its weight

Opinion

CAN CANADA CLEAN UP IN CLEAN-TECH? Canadian Clean Tech Coalition report says yes! (By Shawn Lawrence)

DEPARTMENTS

BIOSIMILAR BATTLEGROUNDS In a follow-up to an article that ran in the May issue of Biotechnology Focus, Noel Courage discusses what is new in biosimilars and where (By Noel Courage)

IN EVERY ISSUE

RESEARCH NEWS

BUSINESS CORNER

28 CALENDAR OF EVENTS

6 R&D NEWS

U of S researchers building cheaper, more efficient organic solar cells www.bioscienceworld.ca

INNOVATOR/SPOTLIGHT With the success of its lead blockbuster drug Incivek,Vertex Pharmaceuticals is defying trends and expanding its operations in Canada (By Shawn Lawrence)

THE LAST WORD Wanted: A champion for home-grown Canadian biopharma (By Robert Foldes)

DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 3

PUBLISHER’S NOTE

PUBLISHER/ EDITOR-IN-CHIEF STAFF WRITERS

Let’s be stronger together

recently had the privilege of attending an event in Toronto hosted by Life Sciences Ontario and Biopolis Québec. The event, Connecting Life Sciences Across The Ontario - Québec Corridor, included plenary sessions and seminars, with key guest speakers and thought-provoking panel discussions focusing on the power of the Ontario-Québec Corridor. Some of the themes at the event centered on questions like who the key individuals are that need to be engaged in the corridor and how can our two provinces work together to promote themselves. The answer was simple: investors, innovators and government all need to be engaged in the process. It was interesting to hear what the Corridor was about and what the plans were for it going forward. Even more impressive was the message that things are already happening with the two sides actively collaborating in areas of common benefit to broaden the collective life sciences community. With the framework of the agreement established, it’s now all about taking the next steps. The priority, according to many of the presenters, is populating the corridor, encouraging companies, researchers, academia et al to use the MOU to their advantage and work with one another. Already, concrete examples of joint projects and talk of future partnerships in the business community are being discussed and implemented. For example, the Québec Consortium for Drug Discovery (CQDM) used the event to announce that it was funding two joint Québec/Ontario research projects in biomedical research for a total of $1.5M. “This investment provides an opportunity to strengthen biomedical research in Québec and Ontario by the alignment of scientific and business resources”, said Max Fehlmann, president and CEO of CQDM. The selected projects are orientated toward the development of new tools that will accelerate the discovery of more efficient and safer drugs. The projects have been evaluated by an international panel of experts for scientific excellence, innovation and impact on biopharmaceutical research. Each project will be funded with a $750K grant from CQDM. The establishment of this new pilot competition was made possible on the Ontario side by MaRS Discovery District and MaRS Innovation. While the partnership is encouraging, it is but only the first of what is hoped to be many. Moreover, all involved in the Corridor recognize that its success will not happen overnight. As Gord Jans of PriceWaterhouseCoopers stated, this is a long term initiative that still needs support. “It could take more than a billion dollars a year to make it commercially relevant.” he said. Put quite simply, the Corridor is an opportunity to create a powerful brand to both tell our story to the world and to attract investment. The onus is on all to make it work.

Terri Pavelic Shawn Lawrence Christopher Rogers

CONTRIBUTING WRITERS

John Cho

Louis Lao

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; Brad Guthrie, Alberta Advanced Education and Technology; Carol Reynolds, Genome Prairie; Ulli Krull, UTM; John Kelly, Erie Innovation and Commercialization; Peter Pekos, Dalton Pharma Services; Brad Thompson, Oncolytics; Darrell Ethell, CanReg; John Hylton, John H. Hylton & Associates; Robert Foldes, Cognovie Inc.; Grant Tipler, RBC; Randal R.Goodfellow, P.Ag., Senior Vice President, Corporate Relations, Ensyn; Bob H. Sotiriadis, LLB, a partner with Leger Robic Richard; Dale Patterson, Genome Canada; Darcy Pawlik, Syngenta Seeds Canada Inc; Gail Garland, OBIO; Barry Gee, LifeSciences British Columbia; Bonnie Kuehl, Scientific Insights Consulting Group Inc. 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.bioscienceworld.ca E-mail: biotechnology_focus@promotive.net Subscription rate in Canada $35/year; USA $60/year; other countries $100/year. All rights reserved. No part of this publication may be reproduced without written consent. Publications Mail Registration Number: 40052410 Return undeliverable Canadian addresses to: circulation dept – 24-4 Vata Court, Aurora, Ontario L4G 4B6 National Library of Canada ISSN 1486-3138 \ All opinions expressed herein are those of the contributors and do not necessarily reflect the views of the publisher or any person or organization associated with the magazine.

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

4 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

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R & D NEWS U of S researchers building cheaper, more efficient organic solar cells

Clinical Trials & Patents Helix BioPharma Corp. (Toronto, ON) announces that the “clinical hold” on its investigational new drug application for its Topical Interferon Alpha-2b, Phase 2/3, low-grade cervical lesion efficacy trial has been removed by the U.S. Food and Drug Administration (FDA). The proposed trial is planned to be a randomized, double-blind, vehicle-controlled study in patients with cervical intraepithelial neoplasia grade 1 or 2 lesions (CIN 1 or CIN 2 respectively). The intended sample size is 492 female subjects to be randomized in a 2:1 ratio of active to control. Eligible women will be premenopausal subjects aged 18 to 55 years at screening, with histologically-confirmed CIN 1 or CIN 2 on colposcopic directed biopsy at screening and high risk human papillomavirus (HPV) infection upon the Hybrid Capture® 2 HPV-DNA test. The proposed primary study endpoint will be the resolution of CIN 1 or CIN 2 at month 12, determined by colposcopic directed cervical biopsy together with Pap smear cytology free of ASC-H (atypical squamous cells that cannot exclude high-grade squamous status), AGUS (atypical glandular cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesions), HSIL (high-grade intraepithelial lesions), and adenocarcinoma in situ (AIS) or adenocarcinoma. The study is designed with a 12-month overall duration per patient, including treatment and follow-up. Helix plans that the results of its U.S. Phase 2/3 trial and the results of its European Phase 3 trial, if successful, will be submitted together in order to seek U.S. and European marketing authorizations for the product for this indication. n

Ron Steer Researchers at the University of Saskatchewen are working to develop more efficient and cheaper photovoltaic solar cells that could help solve global energy problems by turning traditionally brittle and inefficient organic cells into robust, sturdy sources of energy. “We have proof of our principle that indicates we can make a more affordable and reliable cell, but how efficient will the cells be compared to ones that already exist, that’s the part we’re hoping to succeed with. If we can achieve even the slightest increase, even one or two per cent efficiency of these cells, it could be beneficial to everyone,” explained chemistry professor and researcher Ron Steer. Steer says that making the cells more efficient is a matter of converting the spectrum of light.

“Essentially, if you take blue light in the visible part of the spectrum, this works well in solar cells. If you take infrared, this does not work well. So, what we’ve discovered is a way to convert the infrared light into blue light.” His work is taking place in southern Saskatchewan where more hours of sunlight are available than anywhere else on the planet. Along with parts of southern Alberta, these regions receive around 2,500 hours of bright sunshine per year, or about 1361 KwH. The next steps in the process will be creating cells and testing the research principles. If the cells work, it could revitalize the solar industry and turn the sunniest place on the planet into a working grid of solar energy.

Kingston urologist appointed to Order of Canada

Dr. Alvaro Morales Kingston urologist Dr. Alvaro Morales has been appointed to the Order of Canada in recognition of his contributions to advancing the field of urology, notably in the areas of oncology and sexual dysfunction. During the 1970s while working in the Department of Urology at Queen’s University in Kingston, Ontario, Canada, Dr. Morales hypothesized that infecting the 6 BIOTECHNOLOGY FOCUS

bladder with BCG would provoke an immune system response that would be sufficiently robust to eliminate some bladder tumours. BCG is a live vaccine developed in the 1920s to prevent Tuberculosis in humans. Dr. Morales’ pioneering work formed the basis for registration of BCG as a bladder cancer therapy. Since that registration, he has been anticipating a new generation of therapy. In addition to his work at Queen’s University, Dr. Morales was also the principal investigator in the Phase 1and 2 clinical trials, as well as the first Phase 3 clinical trial of Bioniche’s Mycobacterial Cell Wall-DNA Complex (MCC) – trademarked UrocidinTM

DECEMBER 2011 / JANUARY 2012

Aeterna Zentaris Inc. (Québec, QC) announces that the U.S. Food and Drug Administration (FDA) has granted Jose M. Garcia, MD, PhD an Investigational New Drug (IND) approval for the initiation of a Phase 2A trial to assess the safety and efficacy of repeated doses of the company’s ghrelin agonist, AEZS-130 (macimorelin), in patients with cancer cachexia. The study is a doubleblind, randomized, placebo-controlled Phase 2A trial to test the effects of different doses of the ghrelin agonist, AEZS-130, in 18 to 26 patients with cancer-cachexia. The study will be conducted under a cooperative research and development agreement (CRADA) with the Michael I. DeBakey Veterans Administration Medical Center which will be funding the study. AEZS-130 will be provided by Aeterna Zentaris. n

R & D NEWS

Impact of ethanol industry in Canada assessed in new Conference Board report The Conference Board of Canada has released a study assessing the economic impact of the ethanol industry in Canada, its environmental and health effects, and the balance between the energy required to produce ethanol and the amount of energy generated. The report assessed the economic impact of the ethanol industry, examined the policy objectives that underpin government support of the ethanol industry, and assessed some of the future opportunities for the industry. According to the report, Ethanol production in Canada has reached almost two billion litres per year and will continue to grow because a federal renewable fuel standard has been implemented and transportation fuel markets continue to expand. The study also found that ethanol can contribute to reducing Canada’s greenhouse gas (GHG) emissions. Life cycle analysis - which considers the emissions resulting from each step of production and consumption - indicates that a 10 per cent ethanol blend reduces GHG emissions by four to six per cent compared to gasoline. If a 100 per cent ethanol blend were available,

GHG emissions would be between 40 and 62 per cent lower than those from gasoline production and use, depending on the production technologies and energy sources used. “Good policy is based on accurate information and careful assessment of the alternatives. The purpose of this report is to assess the evidence and to contribute to policy discussions around ethanol,” said Len Coad, director, Environment, Energy and Transportation. “Our study concludes that ethanol should be part of Canada’s energy mix. It is a clean transportation fuel

that has a positive energy balance, reduces greenhouse gas emissions, and contributes to energy self-sufficiency.” The economic impacts of ethanol production and use come from three primary sources: construction of plants, operation of plants, and government financial support of the industry, with the industry’s contribution to the Canadian economy estimated at as much as $1.2 billion annually. Government support in Canada is estimated to average approximately $260 million annually from 2006 through 2012. An estimated $925 million in government revenues is generated during the construction phase for ethanol plants, and annual operations bring another $240 million (estimated) into government coffers. The study was funded by the Canadian Renewable Fuels Association. The findings are based on a thorough review of an extensive range of reports and scientific studies about ethanol technologies, costs, environmental impacts, infrastructure, and policy support, with a particular focus on research using peer-reviewed, scientific methods. The report, Ethanol’s Potential Contribution to Canada’s Transportation Sector (www.conferenceboard.ca/documents. aspx?did=4511), is publicly available from the Conference Board’s e-library (www. e-library.ca).

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DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 7

R & D NEWS Governments of Canada and Saskatchewan strengthen bio-extraction industry Minister Yelich joined by Dr. Jochen Kockler, DLG Exhibitions; Lionel Labelle, STEP; Minister; Minister Ilse Aigner, Federal Minister of Agriculture, Food and Consumer Protection (Germany); Carl-Albrecht Bartmer, DLG Exhibitions, at the Agritechnica 2011. New solvent-recovery equipment being installed at POS Bio-Sciences will improve its capacity to help Canadian industry and international clients bring new bio-based oil ingredients to market with reduced research costs and environmental impact. POS’s clients from the cosmetics, nutraceuticals, food supplement and bio-fuels industries are eager to begin trials using this new equipment. Minister of State for Western Economic Diversification, Lynne Yelich and Minister of First Nations and Metis Relations, Ken Chev-

eldayoff announced a shared investment of $261,000 to purchase and install solventrecovery equipment at POS Bio-Sciences which will achieve more cost-effective extraction processes for oils, proteins, and bio-mass by reducing water and solvent usage. The federal and provincial governments are each contributing $130,500 through the Canada-Saskatchewan Western Economic Partnership Agreement (WEPA) to the equipment purchase and installation. POS Bio-Sciences is providing the balance of

the project funding which totals $440,000. POS Bio-Sciences will purchase and install a custom-designed, explosion-proof solvent condenser along with two storage tanks and a chiller system tailored to POS specifications for biomass and microalgae extraction. Installation is expected to be complete in summer 2012. Solvents in the bio-extraction process are costly, challenging a company’s ability to achieve price point competitiveness. POS’s new equipment will minimize the amount of solvent required in the extraction process, thereby reducing production costs and increasing the profitability of product development. “This equipment will be of great interest to a broad spectrum of companies in both food and non-food industries, predominantly those with an interest in extraction of biomass such as microalgae, yeast, and bacteria,” says Dale Kelly, POS president & CEO. “The extraction technology for biomass is in its very early stages and its potential spans far beyond the early identified uses, into the future.”

Finding E. coli’s Achilles heel Thanks to the work of a Simon Fraser University researcher and two of his students, science is closer to finding a new way of combatting infections caused by Escherichia coli (E. coli) and other related bacteria. SFU molecular biology and biochemistry (MBB) associate professor Mark Paetzel and his students Kelly Kim and Suraaj Aulakh have discovered how two proteins bind together in the outer membrane of E. coli. The Journal of Biological Chemistry has just published their findings on-line in the paper Crystal structure of the β-barrel assembly machinery BamCD complex. Like many disease-causing forms of bacteria, E. coli bacteria are becoming increasingly resistant to conventional antibiotics. However, Paetzel, Kim (doctoral candidate) and Aulakh (master’s candidate) believe E. coli’s dependence on a factory-like machine in its outer membrane to keep it alive provides science with an untapped Achilles heel.

The two proteins (BamC and BamD) in E. coli’s outer membrane bind together to help form what is known as the β-barrel assembly machinery (BAM) complex. Once up and running the complex ensures proper formation of proteins in the outer membrane, which serves as a protective barrier for E. coli. These outer membrane proteins can function as foot soldiers that ensure E. coli’s survival by helping it to penetrate and attack its hosts, fight antibiotics and accomplish other tasks. If Paetzel and his team isolate how the BAM complex’s other proteins bind together and collectively kick-start the complex’s protein-assembly-mechanism they’ll have cornered E. coli’s Achilles heel. “Being able to see and understand how this happens would enable us to design inhibitors to stymie the complex’s formation and startup,” adds Kim. “It would be like watching a molecular

8 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

movie in real time and designing a monkey wrench, effectively a new form of antibiotics, to shut down or cripple the complex before it starts functioning,” said Aulakh. The researchers hope the BAM complex could be a potential new drug target to help fight many diseases, such as meningitis and gonorrhea, which are also caused by BAM-containing bacteria.

BUSINESS CORNER Amorfix and Helix Biopharma partner to develop cancer therapeutics Amorfix Life Sciences, a product development company focused on diagnostics and therapeutics for misfolded protein diseases, is collaborating with Helix BioPharma to develop therapeutics against cancers associated with mis-folded prion protein. The therapeutics will specifically target tumour cells and are hoped to be more effective and safer than traditional cancer treatments. Antibodies can be effective as therapeutics by delivering a toxic payload directly to the tumour. As part of this collaboration, Amorfix will provide tumour specific antibodies identified and developed with their proprietary ProMIS discovery technology while Helix BioPharma will utilize their proprietary technology to produce antibodyurease conjugates which are toxic to cells. “This collaboration represents an important combination of technologies required

to produce new therapeutics for the effective treatment of cancer” said Dr. Robert Gundel, Amorfix president and CEO. “We have been very successful in generating high affinity antibodies against disease specific epitopes (DSEs) that show preferred binding to certain tumour cells, but not to normal cells. Our lead misfolded PrP antibody shows selective binding to five out of six human ovarian cancer cell types but does not bind to normal human ovarian tissue. In addition, this antibody binds selectively to four out of six human lymphoma cancer cells but not to normal human lymphocytes.” According to Gundel, ovarian cancer in particular remains an area of very high unmet medical need with a current five year survival rate of less than 50 per cent. “By attaching Helix’s urease toxin to our antibody, we are providing an effective means for specific delivery directly to the

tumours, and not subjecting normal cells to the toxin. We are very pleased to have Helix BioPharma as a partner for this program as their conjugation technology and experience with the urease system is an important component for the overall success of the project.” Details and/or financial terms of the collaboration have not been made public.

Eisai Ltd opens its doors in Canada Eisai Limited, a wholly-owned Canadian subsidiary of Eisai Inc., officially celebrated its introduction to the Canadian healthcare marketplace at a celebration last month in downtown Toronto. Attendees included patients and advocates, healthcare providers, diplomats and government officials, Canadian employees and corporate executives from Eisai Co. “Establishing our presence in Canada is a significant step in expanding our North American presence,” said Haruo Naito, president and CEO of the Tokyo-based global headquarters of Eisai Co., Limited. “We are pleased to officially introduce the Eisai team to the Canadian healthcare community and to bring our patient-focused corporate mission of human health care (hhc) to Canadians through the provision of our unique products.” With Canadian headquarters based in Mississauga, ON, one of the largest biopharmaceutical clusters and medical communities in North America, Eisai Limited also employs sales representatives located across Canada. “Working together with companies like Eisai, we are building a stronger, more innovative economy and creating jobs,” said Minister of Economic Development and Innovation Brad Duguid. “Our congratulations to Eisai for their leadership in research and new product development.” “We are grateful for the investment from the McGuinty government to help

Eisai Limited officially launched in Canada at a reception in downtown Toronto (left to right): Mr. Eiji Yamamoto, Japanese Consul General; The Honourable Brad Duguid, Ontario Minister of Economic Development and Innovation; Mr. Haruo Naito, President and CEO, Eisai Co. Ltd.; Mr. Andy Ayotte, Founding President of Canadian Epilepsy Alliance; Mr. Takihiro Hirasawa, President, Eisai Ltd. establish Eisai in Canada,” said Takihiro Hirasawa, President, Eisai Limited. Mr Hirasawa adds: “In its first year of business, Eisai Limited has launched two products to the Canadian healthcare marketplace: the antiepileptic agent Banzel™ for seizures associated with Lennox-Gastaut Syndrome, a severe form of epilepsy, and Gliadel®, a chemotherapy wafer indicated for patients with recurrent Glioblastoma Multiforme (GBM), the most aggressive type of brain cancer. We have also created New

Drug Submissions to Health Canada for additional products in the area of oncology and anticipate bringing new products to the marketplace in 2012.” Eisai Limited plans to register and commercialize select products from the Company’s U.S. product portfolio. Over time, additional oncology and neurology products will be introduced to the Canadian market including the anti cancer agent Halaven® for metastatic breast cancer, and a novel agent for the treatment of epilepsy.

DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 9

BUSINESS CORNER

CE mark for Verisante Aura™ opens doors to massive European market Verisante Technology Inc. has received notification of conformity to the European medical device directive, allowing sales of Verisante Aura™ in Europe. Aura™ is a non-invasive optical system designed as a tool to aid medical professionals in the assessment of suspect skin lesions for diagnosis as either skin cancer or a benign disorder in less than two seconds. The device uses Raman spectroscopy to biochemically analyze the skin, providing immediate and accurate results. “Verisante Aura™ is a unique tool that can assist doctors in the efficient diagnosis of skin cancers,” said Dr. Harvey Lui, MD, FRCPC, director of the Skin Care Centre at Vancouver General Hospital, Dermatologic oncologist at the BC Cancer Agency, professor and head, Department of Dermatology and

Skin Science, University of British Columbia, and one of the inventors of the Aura™. Verisante believes the Aura™ will help to automate the current process of diagnosis, allowing rapid scanning of the 20 to 40 skin lesions on at-risk individuals, improving patient outcomes and comfort. “With the rising incidence of all types of skin cancers, innovative tools such as the Aura™, which can potentially be used by general practitioners to evaluate suspicious skin lesions quickly and accurately, will become increasingly important to the heathcare system,” said Dr. Lui. The study used to support the CE Mark application was a six year clinical study completed at the Skin Care Centre at Vancouver General Hospital, where Verisante Aura™ was used to collect data on over

1,000 lesions. The Conformite Europeenne (CE) Mark approval is recognized by all the 27 Member States of the EU and by Australia through a reciprocity agreement. “Obtaining a CE Mark allows us access to a market of over 21,000 dermatologists and 500 million people,” said Verisante president and CEO Thomas Braun. The need for a device such as Aura is pressing specifically in Germany where the incidence of skin cancers has tripled since 1980 and is about 20 per cent higher than the rest of Europe, with melanoma accounting for 2,217 deaths each year. With a population of 80 million, Germany also offers a reimbursement of 150 Euro under their state health insurance which covers skin cancer screenings every two years for people age 35 and older. According to Braun, Verisante intends its initial launch in the EU to begin in Germany, Austria and Switzerland, where distribution channels will be placed to support sales and marketing efforts.    The European medical device market is the second largest in the world, worth over $78 billion and representing 30 per cent of the world market – second only to the United States. The company will also now register Aura™ with the Therapeutics Goods Administration in Australia.

Dealmakers Aeterna Zentaris (Québec City, QC) and Hikma Pharmaceuticals (London, UK) have singed a commercialization and licensing agreement for Aeterna’s lead oncology compound, Perifosine, for the Middle East and North African regions. Perifosine, anoral Akt inhibitor, is currently in two Phase 3 programs for the treatment of colorectal cancer and multiple myeloma in the U.S. and Europe. Under the terms of the agreement, Aeterna Zentaris is entitled to receive an upfront payment and additional payments upon achieving certain pre-established milestones in the aggregate of US$2 million. Furthermore, Aeterna Zentaris will be supplying perifosine to Hikma Pharmaceuticals on a costplus-basis and is entitled to receive double-digit royalties on future net sales of perifosine in the MENA region. Hikma Pharmaceuticals will be responsible for the registration and commercialization of perifosine in the MENA territory. n

Valeant Pharmaceuticals International, Inc. (Mississauga, ON) has signed an agreement to acquire iNova, a private pharmaceutical group which sells and distributes a range of prescription and over-the-counter (OTC) products in Australia, New Zealand, Southeast Asia and South Africa from Archer Capital, Ironbridge n

and other minority management shareholders. iNova owns, develops and markets a diversified portfolio of prescription and OTC pharmaceutical products in the Asia Pacific region and South Africa, including therapeutic weight management brands such as Duromine, as well as leading OTC brands in the cold and cough area, such as Difflam and Duro Tuss. Valeant will pay iNova shareholders $625 million upfront and up to an additional $75 million in potential milestones based on the success of pipeline activities, product registrations and overall revenue. The transaction is subject to certain closing conditions and post-closing adjustments, and is expected to be immediately accretive. Performance Plants Inc. (Kingston, ON) and Shaanxi Hybrid Rapeseed Research Center (SHRRC) of China, have signed a memorandum of understanding (MOU) to co-develop high performance rapeseed varieties to address farmers’ needs in China. The MOU represents a second example of PPI’s strategic business development plan to form global technology and product development alliances for commercialization of its technologies. In mid-July, Performance Plants signed a commercial licensing agreement in corn and a four year R&D agreen

10 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

ment for rice and soybean with a leading Chinese agricultural company, Beijing Dabeinong Technology Group Co. Ltd. (DBN). In addition to containing research and development directions and collaboration terms, the MOU forms the basis for a commercial technology transfer and licensing agreement between the parties. Novadaq® Technologies Inc. (Mississauga, ON), a developer of real-time imaging systems for use in the operating room, has signed exclusive multi-year sales and marketing agreements with Kinetic Concepts, Inc. (KCI) (San Antonio, TX), and its LifeCell business unit, for the commercialization of Novadaq’s SPY® system in additional surgical and wound care applications. The SPY fluorescence imaging system enables surgeons to assess tissue perfusion in real-time during a wide variety of procedures. KCI will pay Novadaq exclusivity payments consisting of $3 million upfront and additional milestone payments. KCI and Novadaq will share on-going sales revenues from SPY Systems and the disposable products required to perform SPY procedures. The new sales and marketing agreements range in length from six to seven years and cover territories including North America, Europe and Japan. n

By: Dr. John Cho and Dr. Louis Lao

CANCER

Figure 1

STEREOTACTIC BODY RADIATION THERAPY IN EARLY STAGE NON-SMALL CELL LUNG CANCER

Figure 2

Figure 3

Radiation therapy is the medical discipline that treats malignant diseases with ionizing radiation. The practice of treating cancer with radiation has been around for more than a century. Shortly following Willhelm Conrad Roentgen’s discovery of x-rays in late 1895, the very first (breast) cancer patient was treated with x-rays in early 1896.

adiation, as a therapeutic modality, is a local treatment. Its efficacy in killing tumour cells depends, amongst others, on dose. However, higher doses also incidentally damage the normal surrounding tissue, increasing treatment toxicity. Empirically, less radiation toxicity was observed if the total dose was divided into smaller doses (i.e. fractions) over multiple days. Fractionation exploits radiobiological differences in cellular repair mechanism between the tumour and normal tissue and is an important means of reducing toxicity and sparing normal tissue. Further normal tissue sparing can be achieved by conforming the radiation dose around the tumour target, reducing the dose to adjacent normal tissue. The degree of conformality is, in part, limited by the technical constraints and associated treatment uncertainty (such as random positioning errors, patient motion, etc.). Radiation oncology is a technical discipline. In the last decade, the field has witnessed tremendous advances both in treatment planning and treatment delivery. This is largely due to more powerful

computers and better imaging devices. These advances allow targeting of tumours in a precise and accurate manner and, consequently, make possible the sparing of adjacent normal tissue.

WHAT IS SBRT? SBRT stands for stereotactic body radiotherapy (also known as SABR, stereotactic ablative radiotherapy). SBRT is a method of delivering ablative doses of radiation safely. Typically, very large doses per fraction (i.e. 7.5-20 Gy) are given over a few fractions (i.e. 1 to 8 fractions over 1 to 2 weeks). Fractionation effects to spare normal tissue become less important with larger fraction sizes. By necessity, the dose gradients must be very sharp and tightly conformed around the tumour target in order to limit the dose spilling into the surrounding normal tissue (Figure 1). SBRT represents the culmination of several important technological developments in radiation therapy. These technologies constitute essential components of a SBRT treatment and allow clinicians the ability to target the tumour precisely and accurately so that each treat-

DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 11

CANCER

ment fraction will be delivered as per the intended treatment plan. Major technological developments which allow lung SBRT to become possible include: 4DCT in treatment planning and image guidance radiotherapy (IGRT) during treatment delivery. Adoption of IMRT (intensity modulated radiotherapy, Figure 2) and more recently VMAT (volumetric modulated arc therapy) in treatment planning have also allowed improved treatment conformity and reduction in treatment times.

4DCT

SBRT stands for stereotactic body radiotherapy (also known as SABR, stereotactic ablative radiotherapy). SBRT is a method of delivering ablative doses of radiation safely. Typically, very large doses per fraction (i.e. 7.5-20 Gy) are given over a few fractions (i.e. 1 to 8 fractions over 1 to 2 weeks).

One of the challenges in targeting a tumour in the lung is tumour motion. Under normal conditions, the tumour moves with respiration and the exact amount and direction varies between each individual. In the past, clinicians account for this by setting a generous empiric safety margin to avoid missing the tumour (in the majority of patients). However, this result in overtreatment of tumours with minimal motion while other tumours with significantly more respiratory motion than expected could result in a geographic miss. 4D CT imaging captures dataset in all phases of respiration and can visualize the respiratory excursion of a tumour for an individual patient. An individualized treatment plan can be designed with tailored target margins, taking into account the individual’s tumour motion. This reduces the risk of missing the tumour with significant motion as well as minimizes the irradiated volume of normal tissue such as lung.

IGRT Imaging allows precise and accurate localization of tumour and critical normal structures both at treatment planning and also during treatment delivery. Imaging devices such as cone beam CT co-mounted on the treatment unit’s gantry allow imaging of the tumour at the time of treatment, usually just before (and/or during) the treatment (Figure 3). Thus, the position can be verified prior to each fraction and any misalignments are corrected. Greater confidence in correctly targeting the tumour allows tighter margins and minimizes irradiation of normal tissue such as lung.

WHAT ARE THE BENFITS OF SBRT? Currently, the standard treatment for early stage non-small cell lung cancer (NSCLC) is surgical resection. Surgery offers 80-90 per cent local tumour control rates and five year overall survival rate of approximately 12 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

70 per cent.¹ However, some patients with resectable early stage NSCLC are elderly with significant co-morbid illness, particularly lung disease from smoking, and are deemed “medically inoperable” due to unacceptably high operative risk. In the past, these medically inoperable patients are either: treated with conventional radiotherapy or observed without any treatment. Given sufficient time, all else being equal, untreated tumours will progress and, eventually, become incurable. Conventional radiotherapy offers lower local tumour control rates in the order of 30-40 per cent² Tumour control rates reported in SBRT series are comparable to those reported in the surgical series with local control rate in the order of 80-90 per cent.³ Inoperable patients with potentially curable, resectable disease can now be offered this potent, non-surgical treatment alternative. SBRT is non invasive and very well tolerated. Very frail patients with poor pulmonary function have been safely treated. Since very little normal lung tissue is treated, the treatment is safe with a very modest side effect profile and major complications are extremely uncommon. Treatment is given as an outpatient and therefore no hospital stay is required. Furthermore, the treatment course for SBRT is also much shorter (compared to conventional RT). A typical SBRT treatment takes only one to two weeks where as conventional radiotherapy generally takes six to seven weeks. This has a significant impact on patient compliance and convenience, especially in this frail, elderly patient population. In addition, they may live a long way away from the treating hospital and transport may be an issue. From a health economics perspective, the lack of hospital stay and the much shorter treatment course also translates into a more cost effective treatment which reduces the burden on an already heavily stretched health system. Studies have shown that SBRT is more cost effective than conventional lung radiotherapy.4

EFFECTIVENESS AND SAFETY OF SBRT Numerous single and multi-institutional studies have shown that SBRT for early stage non-small cell lung cancer is safe and effective. These studies have consistently shown long term tumour local control rates of 80-90 per cent and low rates of toxicity.

CANCER

The excellent local control rates reported for SBRT is extremely encouraging as this represents significant improvement when compared to historical conventional radiotherapy series and are comparable with control rates reported in the surgical series. Princess Margaret Hospital reported a series of 108 patients with early stage non-small cell lung cancer treated with SBRT and the four year local control rate was 89 per cent. The most common side effects which occur during treatment include fatigue (50 per cent) and shortness of breath/cough (36 per cent) and vast majority of these were mild and manageable. Significant acute or late toxicities were rare (grade 3 early toxicities =4, grade 3 late toxicities =6, no grade 4 or 5 toxicities observed). 5

WHAT ABOUT SBRT FOR OTHER TYPES OF CANCER? The concept of SBRT was first developed in Europe in the 1990s, modeled on stereotactic radiosurgery of brain tumours. Early stage non-small cell lung cancer was the first extracranial tumour site treated with SBRT and, thus, most of the experience and evidence supporting SBRT is for this site. With early success in treating primary lung cancer, SBRT is now also used to treat metastatic deposits in the lung from other cancers (such as colorectal, sarcoma, and breast). There are also emerging data treating other disease sites using SBRT. Currently most of the experience in using SBRT is in the area of lung, liver, spine and prostate. Different organ sites present different considerations

and challenges which need to be overcome but as clinicians gain more experience and confidence in using this technique there will be more widespread adoption of SBRT in treating other cancers.

WHAT CAN WE EXPECT IN THE FUTURE? There is great interest in expanding the indications for lung SBRT. SBRT has not been rigorously compared, head to head, with surgery in a study but there is currently an on-going prospective randomized study comparing SBRT and surgical resection for borderline operable early stage NSCLC patients (ACOSOG Z4099/RTOG 1021). Other areas of active research include: defining the dose limiting toxicity in more centrally located tumours (as early experience have suggested increase risk in treating centrally

In summary, SBRT is an effective, non-invasive, safe treatment alternative for medically inoperable patients with early stage nonsmall cell lung cancer. For operable patients, the available data suggest that SBRT may offer comparable tumour control rates but this remains to be proven in a randomized trial. SBRT represents a major advance in radiotherapeutic technique and a new paradigm in the treatment of cancer. SBRT has become a potent tool in the radiation oncologist’s armamentarium and we are likely to see the application of SBRT to many different types of cancer in the very near future.

REFERENCES 1. Narsule CK, Ebright MI, Fernando HC. Sublobar versus lobar resection.The Cancer Journal .2011;17:23-27. 2. Rowell NP, Williams CJ. Radical radio-

There is great interest in expanding the indications for lung SBRT. SBRT has not been rigorously compared, head to head, with surgery in a study but there is currently an on-going prospective randomized study comparing SBRT and surgical resection for borderline operable early stage NSCLC patients (ACOSOG Z4099/RTOG 1021). located tumours with the current dose fractionation), exploring the safety of treating larger tumours beyond the current size limits (>5cm) . There are also studies seeking to improve the accuracy of treatment response assessment.

therapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax 2001;56:628-38. 3. Dahele M, Brade A, Pearson S, et al. Stereotactic radiation therapy for inoperable, early-stage non-small-cell lung. cancer CMAJ 2009;180:1326-28. 4. Lanni TB Jr, Grills IS, Kestin LL, et al. Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractionated radiation therapy for medically inoperable non-small-cell lung cancer.Am J Clin Oncol.2011;34:494-8. 5. Taremi M, Hope A, Dahele M, et al. Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients. Int J Radiati Oncol Biol Phys 2011 Mar 4 [Epub ahead of print].

For more CANCER information visit our DRUG DISCOVERY Web Portal at www.bioscienceworld.ca DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 13

By: Shawn Lawrence

CLEAN TECH

CAN CANADA CLEAN UP

IN CLEAN-TECH? Canadian Clean Tech Coalition Report says Yes!

The second annual Canadian Cleantech Summit was held recently in Ottawa and along with it came the release of the 2011 Canadian Clean Technology Industry Report.

upported by the Canadian Clean Technology Coalition and authored by Analytica Advisors, the report provides in-depth insight into the industry, ranking Canada in a global context and grading it in terms of its revenue and employment numbers. The findings of the report may surprise some. Currently, Canada’s clean technology industry already employs 44,000 (in close to 700 clean tech companies) and remarkably generates half of its sales from exports. Further, Canada is home to a clean tech industry which produces $9 billion in revenues. This figure is impressive when one considers the fact that Canadian spending on clean-tech infrastructure pales in comparison to the big global players in the sector including Japan, Germany, China and Korea. Most impressive is that despite a global financial environment were most industries are stagnating or struggling, the report indicates that Canada’s clean tech industry is showing remarkable growth. The coalition, which has been in existence for 18 months, compiled the report together with entrepre-

14 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

neurs, investors, information providers, program developers and policy makers out of a necessity to provide an aggregate report on the industry. “We are a policy based coalition, and the report is there to pre-broker policy recommendations, to put a view forth from the perspective of a very diverse group,” says Céline Bak, partner at Analytica Advisors and co-founder of the Canadian Clean Technology Coalition. Bak explains that because clean tech is a relatively young industry and that it is not really recognized as an industry at the federal level, there was a need for a body or group to help educate decision makers on what clean tech in Canada was about and why supporting it as an industry should be a priority. “The clean tech sector is predominantly made up of small and medium-sized enterprises (SMEs) and SMEs in general are not top of mind when policy decisions are made and programs are developed because they don’t engage with government and the reason for that is they don’t have the time. Through the coalition, we bridge that gap, through this taxonomy we’re here to present the industries potential as a whole and to do it in a way that makes sense to government.” By building a policy consensus across SMEs, large technology adopters and financiers, the Coalition’s and the report’s value comes when it can make this clear case to all levels of government. The report also has other uses she adds including as both a competitive and promotional tool here in Canada and abroad. “CEO’s in the sector can use this report as a benchmark for their growth, and to compare their performance and investments in R&D and commercialization as well as a means to attract investment from abroad.” In terms of the report itself, the Canadian Cleantech industry was broken down into nine sectors: Biofuels and Bioenergy, Energy Efficiency, Energy Infrastructure, Industrial Processes, Power Generation, Recycling and Recovery, Remediation and Soil Treatment and Water and Wastewater. These sectors were divided across three segments: Upstream, Downstream and Water. “Upstream is about the production of energy, downstream is about the use of energy and then water is about the use and treatment of water whether its puri-

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CLEAN TECH market share, which could if it continues to grow at its current rate, increase its global market share to two per cent by 2020 and that represents a $60 billion industry.” In addition to functioning as a resource for entrepreneurs, investors and policy makers who are now or may be engaged in the industry, the report also goes a step further making recommendations on how to position the sector as both a beneficiary and catalyst for future economic growth. While there were areas of strengths, specifically in terms of performance there remain a number of factors requiring urgent improvements, for which the report made several recommendations.

The recommendations made in the report were:

“The clean tech sector is predominantly made up of SME’s and SME’s in general are not top of mind when policy decisions are made and programs are developed because they don’t engage with government and the reason for that is they don’t have the time. ” – Céline Bak

fication or water processing.” Each sector and segment was graded according to strength and for potential growth on a macro and micro level. Overall, the report gave the industry a grade of ‘B minus’. “Canadian clean technology companies have proven their competitiveness by posting a compound annual growth rate (CAGR) of 19 per cent during the recession, and they grew by 56 per cent in 2010,” says Bak. She adds that the industry’s rate of growth stacks up strongly in comparison with the growth cycles of most of the other older more established industries in Canada. “The Canadian Cleantech Industry is approximately 15 years old on average and is taking shape in a way that is very similar to previous Canadian based innovation industries, whether the comparable is the biotech sector, the mining sector or the aerospace and defence industry. However, it is enjoying more rapid growth, specifically the Canadian clean tech industry has generated revenues in just 15 years, what took the aerospace and defense industry to obtain in 20.” Impressive numbers to be sure, but even more impressive is the Coalition’s belief that Canada’s clean tech industry can be a $60 billion industry with a workforce of 125,000 by 2020. The numbers shown in the report seem to support this theory “We have concluded that currently the global market demand of the industry is estimated at one trillion dollars, and that overall, the global industry will grow at an 11 per cent compound annual growth rate. This means it will triple by 2020 and become a three trillion dollar global industry. Comparatively, the Canadian industry at the moment has one per cent of global

16 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

• Realization of Economic and Productivity Potential of the Clean Technology Industry – Make clean technology a cornerstone of Canada’s policies for economic productivity, energy, innovation, exports and the environment. Adopt strict environmental regulations to induce innovation and industry strength (Porter Hypothesis)iii. Create a virtuous cycle leading to jobs, sustainable growth, exports and labour productivity. • Development of Domestic Market for Clean Technologies – Foster access to public and private domestic markets by globally competitive SMEs. Providing opportunities for domestic deployments and referrals will make it possible to convert the world’s openness to Canadian clean technology into export sales. Support incubation of companies by entrepreneurs. • Development of Financial Markets Specific to Clean Technology – Accelerate the development of financial markets for equity, debt, export and buyer finance. • Engagement with International Financial Institutions – Establish strategies to engage with International Financial Institutions as a foundation for exports to high growth economies and to low and middle-income countries. • Leverage Export Expertise and International Reputation – Capitalize on the respect SMEs enjoy in the US, and leverage the respect that Canadian companies enjoy in international markets. • Engagement with Multinational Enterprises – Strategically engage with multinational enterprises, particularly in high growth regions. These recommendations are considered integral to reaching the $60 billion goal explains Bak. “We know that this is an industry that is evolving very quickly, I’d go so far as saying its set to explode, but more can be done to facilitate this process. This includes duplicating the model that countries who are leading the way are using,” says Bak. Bak highlights countries like China, Korea, Germany and Japan as examples to follow because they have

CLEAN TECH a more integrated approach in growing this industry compared to Canada. “They’ve managed to find a way to connect international development, domestic labour production, as well as their employment and innovation agendas more comprehensively than we have here. They’ve also done so with coordinated policies both in the public and private sector.” The fact that the Canadian Cleantech sector has achieved growth to this point in the absence of a robust information and policy environment is truly fascinating says Bak. So how have Canada’s clean tech companies managed to do it? For starters, under the current landscape, nationally almost all clean tech companies rely on federal Scientific Research and Experimental Development (SR&ED) tax credits. Likewise, the industry has benefitted also from funds such as the Clean Energy Fund, the EcoEnergy Technology Initiative and stimulus investment such as the Canmet Energy and Sustainable Development technology Canada (SDTC). At the provincial level, the industry has also had its backers for the most part. In BC where the largest number of clean tech companies in the country per a capita can be found, the industry is helped along by strong regulatory policies as well as several provincial investment funds. Likewise in Ontario, the province’s Green Energy Act coupled with support from the Ministry has helped the industry along. “The Ontario government did invest a considerable amount of policy time to understand the industry, they used information that we produced in the 2010 STCC Clean technology growth and go to market report which was the precursor to this year’s national report.” Various other provinces are using the information to set policy in and around clean-tech especially in the Prairie provinces where biofuel initiatives are many and in Quebec where there is heavy investment in renewable energy, biofuels and waste management. One area the industry is also doing well in is in revenues from exports. While exports are traditionally an area where other biotech industries have struggled, 81 per cent of companies in the clean tech space are engaged in export activities. Yet this is also an area that the Coalition concludes could stand to be improved upon. “We’re good at exporting by virtue of our small domestic market. Our companies are born exporters, as most will make their first sale outside of Canada. While it’s one of our strengths, it’s also one of our weak points because like in many industries in Canada, the majority of the companies in this sector are small and medium sized enterprises. So it’s not the majority of companies in Clean tech generating revenue from exports, most are too small to capitalize on export opportunities.” As such, Bak says the report emphasizes the need for more procurement programs similar to the $40 million Canadian Innovation Commercialization Program to grow and promote the SMEs.

“There is a need to establish a domestic market for Clean Technology. One of the things that we know well about Canada is that we are very cautious adopters of new technology, and some people might go as far as to say that our idea of developing a business case for the adoption of new technology consists of counting the number of deployments that exists in the U.S. We don’t actually take the time to consider new technology on its own merits and figure out for ourselves how it would make sense from a business perspective, and what the benefits are and how to quantify those. The recent Jenkins report made very clear in both its main report and the procurement report that you can’t have an innovation strategy for a country without some attention being paid to strategic procurement of technology. The Jenkins report also made it very clear that one cannot underestimate the importance of a signal from the federal government as a strategic procurer of technology from SMEs. For technology companies, procurement for technology companies is all about references, and the ability to use those references to establish credibility internationally. That’s not to say we forget our focus on exports, but the impact would be huge with relatively little investment in domestic procurement for companies who are already very focused on export markets. The end result would be to look stronger in the eyes of potential foreign buyers.”

For more CLEAN TECH information visit our ENERGY Web Portal at www.bioscienceworld.ca

“The Canadian Cleantech Industry is approximately 15 years old on average and is taking shape in a way that is very similar to previous Canadian based innovation industries, whether the comparable is the biotech sector, the mining sector or the aerospace and defence industry.”

DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 17

By Shawn Lawrence

COMPANY SPOTLIGHT

Laval site a key cog in

VERTEX PHARMACEUTICAL’S Expansion of Vertex GRAND PLAN Canada defying the trend

In 2009, Vertex Pharmaceuticals Inc. pulled off one of the bigger Canadian biotech deals in recent memory when it acquired Canada’s ViroChem Pharma for $375 million in cash and stock. Many worried at the time that the takeover would signal lost jobs and that the Laval, QC site would inevitably be closed down. In the end, those fears were proven wrong. In fact, the Cambridge, MA based company chose to go an entirely different route, not only keeping the site open, but using it as its launch pad into the Canadian marketplace.

What has made the transition into Canada easier is the fact that Vertex has experienced a great deal of success at the international level. In May, the U.S. Food and Drug Administration approved Vertex’s first medicine, Incivek, for the treatment of hepatitis C (HCV). The drug itself is considered a blockbuster. It is a protease inhibitor for the treatment of chronic HCV infection. Specifically it treats patients with genotype 1 chronic hepatitis C (HCV) with compensated liver disease, including cirrhosis (scarring of the liver). The drug is to be used in combination with pegylated-interferon and ribavirin in both treatment-naïve and treatment-failed patients. For Vertex, the approval marked the proverbial game-changer, vaulting the company from a promising biotech with a compelling pipeline to a full-fledged biopharma operation. By October, this product was also available for sale in Canada. Suddenly, the strategic decision to keep the scientific research facility in Laval as a footprint in Canada was justi-

18 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

fied and Vertex moved to build its marketing and commercial operations across the rest of the country. Additionally, Vertex has transformed the facility into one of its five global scientific research sites. Moreover, the company has acted on plans to expand the facility’s capabilities towards research of other diseases. Lastly, the company has embraced a plan to use the Quebec site to tap into Canada’s largest biopharmaceutical hub. As vice president of Research and Development at Vertex Canada, Youssef Bennani is responsible for research and clinical development activities in Canada emanating from the site. Bennani says there are many things to like about the location in Laval, beginning with its proximity to one of Canada’s largest biotech and science clusters Montreal. “On the science side there is a high density of pharmaceutical companies. There’s also a strong presence here in immunology with a deep pool of talented researchers. We want to capitalize on all of this from a R&D per-

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COMPANY SPOTLIGHT

“On the science side there is a high density of pharmaceutical companies. There’s also a strong presence here in immunology with a deep pool of talented researchers. We want to capitalize on all of this from a R&D perspective and also from a collaborative angle. There’s also plenty of access to patient care-givers and clinicians in Canada that we’d like to tap into that as well.” — Youssef Bennani

spective and also from a collaborative angle. There’s also plenty of access to patient caregivers and clinicians in Canada that we’d like to tap into that as well.” In terms of acting as a hub or a base for Vertex’s commercial operations in Canada, he says geographically the location makes plenty of sense. “Our location keeps us in close proximity to the other players in the game, so it suits our business needs too and gives us easy access to all the major Canadian markets.” Bennani adds that in Canada there is huge market potential for Incivek. “It’s pretty significant as there are over

20 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

250,000 Canadians who are infected with this virus, and our drug showed that 80 per cent of people with G1 HCV that are treated with our drug are cured, many within a shorter period of time.” With tremendous growth since the takeover, the company is also trying to position itself to support future product launches in Canada. This is being accomplished by increasing the manpower of its commercial and regulatory affairs teams. For example, Vertex is also developing several novel agents for treatment of cystic fibrosis (VX770 and VX-809). These treatments were discovered at the company’s San Diego research center and developed by Vertex’s clinical teams in Cambridge, MA. There is also early stage work at other Vertex centers on rheumatoid arthritis and epilepsy, while not as far along as other products in the pipeline, could one day have commercial potential. The acquisition of ViroChem also gave Vertex access to two pipeline drugs that could offer a big assist in creating cocktail therapeutics for hep C patients. “We like most businesses are always on the lookout for good opportunities and ViroChem had several assets we were interested in and one in particular which was an experimental hepatitis C virus (HCV) polymerase inhibitor VX-222. Vertex Pharmaceuticals sees combination treatments as the future of hepatitis C treatment, just as is the case with HIV already, so we jumped at the chance to add this drug. Currently we have VX-222 in a Phase 2 trial in combination with Incivek and the hope is that together they will provide even greater cure rate for patients with HCV.” It’s safe to say, that there is a lot of activity happening at the Laval centre. Unlike many companies in the area who have chosen to scale back operations, Vertex Canada has defied this trend going into full hiring mode. In all, there are now 60 employees at the Laval site, including 42 research scientists. Since August alone the company has hired

COMPANY SPOTLIGHT “Our scientific endeavors, discoveries and findings lead the enterprise. Many companies will put more emphasis on the marketing and commercialization aspect of things. Our goal here is to be first or best in class, we are research driven rather than marketing focused. We aim to address unmet medical needs in severe diseases and things where we can have a major impact on the patient population regardless of market size.” 16 people. Bennani adds there is sufficient infrastructure and research space in place as well as a need for future growth in the company. On how the Canadian Centre operates within the greater Vertex organization, Bennani explains Vertex Canada is fully integrated with the rest of Vertex and its global research strategy. Meaning it works with the other Vertex global sites in Cambridge, San Diego, California, Coralville, Iowa and Abingdon in Britain. The only difference being that research wise it is focused on Crohn’s disease and Colitis. “While we do have a focus that is distinct from the others in terms of our disease focus, we still speak the same scientific language, use the same operating principles and philosophies, and follow the same R&D initiatives. I have projects here involving folks in San Diego, Cambridge and in the U.K. and vice versa. We’re not a separate entity that is on its own.” Researchers at the Laval site are trying to figure out why that is by exploring the genetic markers for both diseases. The choice to focus on Crohn’s disease and Colitis is no accident explains Bennani. “It very much had to do with facilities capabilities as well as the added caveat that both are diseases that are very prevalent in northern countries like Canada. Moreover, the researchers that we brought on board from ViroChem following the take-over were also given the opportunity to suggest the types of research they wished to pursue and in light of the strengths of the facility be-

cause it’s very much an unmet need, these were diseases they suggested.” This openness is an aspect the company prides itself on. “Our scientific endeavors, discoveries and findings lead the enterprise. Many companies will put more emphasis on the marketing and commercialization aspect of things. Our goal here is to be first or best in class, we are research driven rather than marketing focused. We aim to address unmet medical needs in severe diseases and things where we can have a major impact on the patient population regardless of market size. We call our approach a science focused culture which means science plays a significant role in driving our business decisions rather than the other way around.” Vertex has created a number of programs to support its science-focused culture. Among them are the Science and Technology Exchange Program (STEP-OUT) which provides Vertex researchers with the opportunity to take a break from their current role and explore a new scientific area of interest for a three-month period. Vertex also recognizes scientific excellence with its Outstanding Research Award, which is given each year to the Vertex researcher who performs the most innovative scientific work. Additionally, Vertex scientists frequently work with other research collaborators, including academic institutions, non-profit foundations and other companies. Vertex also recently introduced two programs to help scientists learn more about and stay connected to the commercial part of the

company: a ride-along program that enables researchers to shadow sales representatives for a day and another that ensures scientists are included on interview teams that select commercial employees. For these types of initiatives, Science magazine verified Vertex’s status as a top employer, naming it number one on its 2011 list of top employers in the life sciences. Science cited three top characteristics for Vertex: does important, quality research; is an innovative leader in the industry; and treats employees with respect. It was the second consecutive year that Vertex has been included among the top three companies, and with more than 1,900 employees worldwide it is quite an achievement commented Bennani. “It’s something we strive to achieve in general at Vertex. This business of building a science culture, encouraging employee engagement but it’s not easy to execute. We really try to encourage, support and develop our staff so that they feel part of the equation because the best way to drive innovation is to empower people to do their best. There’s an association between the innovation going on at Vertex and the respect we have for our employees. Innovation cannot happen when it’s constrained.”

For more Company Spotlights information visit our PROFILES Web Portal at www.bioscienceworld.ca

DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 21

By: Noel Courage

ACROSS CANADA

BIOSIMILAR Battlegrounds: WHAT IS NEW IN BIOSIMILARS AND WHERE?

iosimilars are second entry biologic drugs. They rely in part on data from an already-approved reference product to reduce the time and cost burden of generating clinical trial data to support their regulatory approval. Biosimilar approvals are analogous to generic pharmaceutical approvals except that biologics are larger and more complex than conventional pharmaceuticals. There is significant controversy about biosimilars and the appropriate data threshold requirements for their approval. This background was covered in an article by Eva Furczon and myself titled: Subsequent Entry Biologics in Canada which appeared in the May, 2011 issue of Biotechnology Focus. The stakes are high for regulators reviewing biosimilar data trying to ensure high similarity of the biosimilar to the innovator product. This is particularly the case for complex products such as monoclonal antibodies used in oncology where the intent is curative and it is an all-or-nothing phenomenon. Switching a cancer patient between different antibody drugs because the biosimilar is not working the same, or as well, as the branded product is a situation to be avoided. Patient safety is a paramount consideration for regulators. The present article provides a brief snapshot of some biosimilar development initiatives in Canada and abroad. 22 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

European Union

Europe, via its European Medicines Agency (EMEA), is leading the way in approving biosimilars and providing guidance to industry. It has published guidelines for six classes of biologics: insulins, granulocytecolony stimulating factors, erythropoietins, somatropins (human growth hormone; HGH), low-molecular weight heparins and interferon alphas. Europe also published draft guidelines in 2010 on a monoclonal antibody class. This is a very significant challenge because antibody drugs are much larger and more complex than single chain recombinant proteins such as somatropin and insulin. At least 14 biosimilars were approved by the EMEA as of Spring 2011, including two somatropins, five erythopoietins and seven granulocyte colony-stimulating factors (filgrastims). Sandoz (a division of Novartis) has three biosimilar products on the market in the EU. Sandoz manufactures biosimilar versions of HGH, filgrastim and human erythropoietin. Teva Pharmaceutical Industries Ltd. is also currently marketing three biosimilars: erythropoietin, filgrastim and HGH. Sandoz has a Phase 2 clinical study on rituximab. Rituximab is a monoclonal antibody directed against a B-cell surface protein. It treats non-Hodgkin’s lymphoma, chronic lymphocytic leukemia

ACROSS CANADA why there has not been more action in Canada. and rheumatoid arthritis. Rituximab is a large and There is not a lot of biosimilar development complex protein for treatment of a potentially lifeactivity by Canadian-based companies. It would threatening disease, so it can be expected to be be in Canada’s benefit to provide incentives enclosely scrutinized by regulators deciding whether courage local companies to continue to invest in to grant biosimilar approval. Merck established Merck BioVentures in Deboth innovative biologic and biosimilar biologic cember 2008 for biosimilar development. In 2010, drug development, particularly where Canada has Merck stated that it had two biosimilar candidates developed unique expertise and has a competiin development and anticipated having five biotive edge. similars in development by 2012. Merck has also It would be in Canada’s In 2008, Apotex announced a biosimilar departnered with the Korean company Hanwha velopment collaboration with Intas BiopharmaChemical Corporation to develop a biosimilar benefit to provide ceuticals Limited and Kwizda Pharma to produce incentives encourage version of etanercept. a biosimilar GM-CSF (Granulocyte-Macrophage Teva has four biosimilars in end Phase 2 clini- local companies to Colony-Stimulating Factor). cal trials: follitropin alfa, glyco - PEG-G-CSF, and SemBioSys and Plantform Corporation are continue to invest in rituximab. Teva also has two other biosimilars in developing plant-based expression systems for end Phase 3 clinical trials. Teva Pharmaceutical both innovative biologic biosimilar production. They each have propriIndustries Ltd. purchased the Ratiopharm Group and biosimilar biologic etary protein-expression systems that are differin 2010 in an effort to expand its generic operaent from the expression systems used by many drug development, tions in Europe, which at that time had received innovator biologic companies (eg. single cell sysapproval for one biosimilar (filgrastim) in the EU. particularly where tems, such as yeast, are most commonly used for Pfizer partnered with Indian biotechnology Canada has developed biologic drugs). Health Canada’s guidance docucompany Biocon in 2010 to market a biosimilar ment states that differences in the manufacturing unique expertise and version of human insulin worldwide. Pfizer exprocess will be considered in the comparability pects to gain approval for its biosimilar insulin has a competitive edge. assessment. It is unclear the extent to which a in Europe by 2012 and in the U.S. by 2015. The plant-based product will be able to rely on ininvolvement of Pfizer in the biosimilar space is of interest to industry- novator product data. Companies will be preparing to address these watchers, since Pfizer has a very strong focus on developing its own regulatory issues. innovator products in conventional pharmaceuticals, not second Cangene Corporation (majority owned by Apotex) manufactures entry products. recombinant therapeutic proteins. Cangene has FDA and Health Another interesting trend is companies well known in other indus- Canada-approved biologics. Cangene has previously developed its tries moving into the biosimilar business, such as Samsung. Samsung own versions of established products using proprietary host systems. has invested between $250 million and $390 million (depending on It has gone through the formal new drug application process but the report) in a partnership with Quintiles Transnational Corp. to could potentially move more towards the biosimilar pathway, for exdevelop biosimilars. ample with its GM-CSF in development. There are a number of other contract development and manufacturing companies with expertise United States in therapeutic protein manufacturing and development that have the Some biosimilars such as somatropin (human growth hormone) potential to partner with other companies. Therapure Biopharma have been approved in the US under ‘old’ laws regulating biolog- Inc. is an example of a biopharmaceutical company with expertise ics. The same pathway has been used by other biosimilars of older in producing therapeutic proteins and biosimilars. biologics. Other examples of subsequent entry biological products It is clear from the above high level view that there is a lot of ongoapproved by the FDA are glucagon, hyaluronidase, and calcitonin ing international biosimilar development. Most of the market leaders salmon recombinant. are based outside Canada. However, there are Canadian companies The US government approved a new, abbreviated pathway for that are working hard to develop a foothold in biosimilar drug debiosimilar approvals in 2010. The FDA is already willing to accept ap- velopment. As with conventional pharmaceuticals, there is enough plications for approval the pathway. Acceptance is on a confidential space in the international biologic marketplace for both brand name basis so we do not know the extent to which there is activity on the companies and biosimilar companies. Canada would only stand to new pathway. Initial regulatory guidance from the FDA on applying benefit from nurturing its expertise in biologic drug development, for biosimilar approval is imminent. Biosimilar companies are watch- preferably leading to a cluster of companies with different, diverse ing developments in the US with great interest. One interesting pair R&D strength in either innovator biologics or biosimilars. of bedfellows announced in December 2011 is innovator Amgen and generic Watson Pharmaceuticals. They will make oncology antibody Noel Courage is a partner in Bereskin & Parr LLP, intellectual property law and drug regulatory law. Thank you to Jaime Holroyd for helping with biosimilars (no biosimilars of Amgen’s products). research for this article.

Canada

Canada published a SEB guidance document in 2010. About the same time, Sandoz received approval for its human growth hormone (Omnitrope). Canada has approved of the general approach taken by the EMEA guidelines. It is fair to say that Canada is open for business to biosimilars. The small Canadian market is of secondary interest to many multinational pharmaceutical companies, which may explain

For more ACROSS CANADA information visit our COMMERCIALIZATION Web Portal at www.bioscienceworld.ca DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 23

NEW PRODUCTS Ultracentrifuges New Optima X Series preparative ultracentrifuges from Beckman Coulter, Inc. incorporate an array of contemporary technical features to enhance the user experience and increase productivity. With a large touchscreen display, the Optima X Series product offers a selection of nine languages while real-time graphing plots speed and temperature over time as a run progresses. Enhanced remote control capabilities allow the ultracentrifuges to be monitored from a personal computer or a smart phone. When powered on but not running, the unit requires the same energy as a 60-watt incandescent bulb, further increasing energy efficiency. Optima X Series ultracentrifuges reach a maximum speed of 100,000 rpm and generate forces up to 802,000 x g. Optima X Series instruments are available in two models – the XE, which delivers all of the basic features required to quickly set up and complete a run, and the XPN, which includes all features of the XE plus networking capability, on-board simulation tools and a variety of customizable security and tracking features. The XE is available in 90,000 and 100,000 rpm configurations, while the XPN is offered in 80,000, 90,000 and 100,000 rpm configurations.

and the pyruvate dehydrogenase complex. Each kit provides highly validated and characterized cellular metabolism immunoassay antibodies, all necessary reagents, and optimized protocols.

www.emdmillipore.com DispoEquilibrium DIALYZER™ The Harvard Apparatus 96-Well DispoEquilibrium DIALYZER™ provides simple and

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reliable techniques to analyze up to 96 equilibrium dialysis chambers simultaneously on disposable dialysis plates. These ready to use equilibrium dialysis plates are convenient and cost effective tools for ligand binding experiments including serum protein binding, protein-drug binding, protein-protein binding and proteinDNA binding assays. Each test well in the plate consists of two chambers separated by a regenerated cellulose membrane with a molecular weight cut off of either 5,000 or 10,000 Daltons. Each chamber holds up to 300µl of sample or buffer. To decrease the dialysis time, the plate needs to be rotated through 360° in a vertical position. Harvard Apparatus can also supply a one or two plate rotator or an eight plate rotator with temperature control.

Titrator JM Science’s AQUACOUNTER® Volumetric Karl Fischer Titrator (AQV-300) is reliable, easy-to-use and has performance features which allows measure of moisture content from low to high concentrations quickly and accurately. Measurements are simple and routine with unsurpassed precision. The AQV-300 has six built-in calculation modes to accommodate solid, liquid and gas samples. It includes a statistics package with one-touch calculations. Four files with preset conditions can be stored in memory and allows instant recall of data for up to 20 samples. A built-in detector monitors titration status and a direct key access allows entry of titration parameters. This compact unit with a very small footprint has balance and computer interfaces for GLP and ISO documentation and it is CE approved. The titrator comes with DVD training movie, plasticized Quick-Start guide for use in the lab, paper and pdf manual. Also included,

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www.beckmancoulter.com MILLIPLEX® MAP Kits EMD Millipore launches three MILLIPLEX® MAP kits for cellular metabolism. Based on the Luminex® xMAP® assay technology platform and cellular metabolism antibodies from MitoSciences®, the MILLIPLEX® MAP kits enable fast, sensitive, simultaneous quantification of multiple cellular metabolism biomarkers involved in fatty acid oxidation

Wireless Logger T&D Corporation introduces its new RTR-505V Wireless Logger. The RTR-505V can measure DC voltages from 0 to 22VDC with accuracy of ±0.5mv and can measure voltage directly or from the output of a wide variety of sensors and instruments. The RTR-505V features a large LCD display, capacity for 16,000 readings, IP64 water resistance and up to four years battery life with the “L” version. Compatible with all TandD RTR-500 Series Wireless Data Collectors, the RTR-505V can be seamlessly integrated into a wireless network with other logger types. They can be monitored locally, through a cellular phone system, or

24 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

complete accessories, download software for transferring results to a laptop or PC, RS-232 cable, and AQUACOUNTER® KF Reagent starter kit.

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NEW PRODUCTS High Consistency Rubber ShinEtsu Silicones of America’s newest HCR (High Consistency Rubber) product line – Sil-X-Shin™ Silicone Elastomers are specifically engineered for extruded tubing and profiles. Sil-X-Shin Silicone Elastomers are available in a wide range of Shore A Hardness–from 30–80−and come in a convenient 10:1 ratio of base compound to catalyst. The most unique advantage of the Sil-X-Shin product line is that one universal catalyst can be used with each of the six bases, providing ultimate flexibility. The Sil-X-Shin series has a single, universal catalyst that cures any of the six bases with less than 10 per cent of the composition. Sil-X-Shin Silicone Elastomers are USP Class VI compliant, and their platinum, additioncure chemistry produces a tight surface finish with few residual by-products.

www.shinetsusilicones.com Batch Controller The new Mettler Toledo IND780 stand-alone batch controller combines advanced batching control technology while adhering to the ISA SP-88 Batch Standard. The IND780batch optimizes batch processes with consistent, accurate material transfers, to minimize material waste and improve batch quality. The flexible stand-alone terminal can be used for single or multi-scale batching applications. With the IND780batch, users can take control of manual processes with dependable recipe management and the ability to handle 999 materials. Tolerance checking, material identification via bar-code input, and operator prompting all help to ensure the operator is guided through each batch. Multi-material automatic batching control

handles up to 28 automatic materials with recipe-specific control, including conditional control tasks, go-to commands, recipe re-scaling, timing functions, and control of discrete inputs and outputs to allow the controller to interact with other equipment in the process.

www.mt.com Slide Imaging System PerkinElmer Inc. launches the VectraTM 2 automated slide imaging system, a turnkey platform that allows true walk-away batch processing of up to 200 tissue sections at a time. Additionally, the Vectra™ 2 addresses the need of scientists focused on biomarker research, pharmaceutical development, clinical research and tissue application test development for validated tissue labeling and automated scoring methodology. The new platform adds HistoRX’s AQUA® technology to Vectra’s unique multispectral and image analysis capabilities. Its unique multispectral capabilities, coupled with the powerful image analysis tool inFormTM, can be used to explore even the most demanding of today’s tissue analysis problems, from multi-analyte in situ cytometric analysis and cell phenotyping to stereology-like analyses of tissue disease states. The technology provides >97 per cent inter- and intra-assay coefficient of variation, giving researchers assurance in the quality of their results. The system supports both tissue sections and tissue microarrays (TMAs) with ease and offers a slide hotel for batch scanning of up to 200 slides. The Vectra platform is empow-

ered by the same multispectral imaging technology that drives over 400 NuanceTM cameras sold to date, giving researchers the ability to analyze multiple fluors/ chromagens in a sample, quantifying each separately and accurately.

www.perkinelmer.com Vessels The Thermo Scientific CryoExtra™ vacuum-insulated, stainless steel vessels are available in four different sizes, from 407 litres to 1,630 litres, accommodating both vapour and liquid-phase storage. These containers minimize top-to26 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

bottom temperature variation, preserving the integrity of critical cryogenically frozen samples. Its innovative lid and neck design, combined with advanced temperature monitoring, reduce temperature fluctuations that occur due to lid openings. Furthermore, the microprocessor-based LN2 level control ensures that liquid nitrogen levels are tightly controlled, and the de-fog function allows easy, push-button sample identification.With the ability to store up to 90,000 1.2 – 2.0 mL vials, the largest of the four CryoExtra models (1,630 liter) has the same external footprint as the 1,350 liter unit. All four CryoExtra containers can accommodate both vertical and horizontal racks, and the Thermo Scientific racking solutions are specifically designed for this vessel configuration, further maximizing capacity.

www.thermoscientific.com Fume Hoods Air Science introduces its new Purair ECO™ line of Energy-Saving Ductless Fume Hoods designed for both chemical and particulate protection over a broad 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. The Purair ECO is available in five standard sizes from 30” wide to 69” wide. www.airscience.com

We don’t go home happy until you do.

Maurice

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and the snow storm

Maurice, our Front Desk Agent, isn’t exactly a huge fan of the snow. And driving in the stuff? He dislikes that even more. But one cold, grey December evening, our intrepid Maurice ventured out into one of the biggest storms of the season. What could have driven him to drive into this tempest? His sense of duty. You see, one of our guests had left an important item behind.

Knowing that a cab wouldn’t make it to the airport in time to reunite our guest with his property, Maurice took matters, as well as a frigid steering wheel, into his own hands. Arriving at the airport with mere minutes to spare, Maurice personally handed the item to our surprised, and extremely relieved, traveller. Proof once again that, even after you’ve left our hotel, you’re still a VIP.

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CALENDAR JANUARY 2-12 January 9–11 Biotech Showcase™ 2012 Venue: San Francisco, CA Email: update@ebdgroup.com Web: www.ebdgroup.com/bts/index.php

January 30-31 Bio Manufacturing Summit Venue: San Diego, CA Tel: (416) 214-1144 Fax (416) 214 3403 E-mail: melissa.youngsing@wtgevents.com Web: www.biomansummit.com

FEBRUARY 2012 February 4-8 Society for Laboratory Automation and Screening 2012 Venue: San Diego, CA Tel: 630-256-7527 Fax: 630-741-7527 Email: slas@slas.org Web: www.slas.org

February 13-14 Bio CEO & Investor Conference 2012 Venue: New York, NY Email: bd_registration@bio.org

Web: www.bio.org/events/conferences/ bio-ceo-and-investor-conference/700-0

Email: info@pittcon.org Web: www.pittcon.org

February 16-20

March 19-21

AAAS Annual Meeting Venue: Vancouver, BC Tel: 202-326-6400 Fax: 202-842-1065 Email: meetings@aaas.org Web: www.aaas.org

BIO-Europe Spring® 2012 Venue: Amsterdam, The Netherlands Tel: 760-930-0500 Email: chundschell@ebdgroup.com Web: www.ebdgroup.com/bes/index.php

February 25 BIOTECanada CEO Whistler Summit Venue: Whistler BC Email: kira.pejemsky@biotech.ca Web: www.biotech.ca/en/default.aspx

February 26-28 BioPartnering North America Venue: Vancouver, BC Tel: 1-831-464-4230 Fax: 1-831-464-4240 Web: www.techvision.com/bpn/

MAY 2012 May 29-30 Biofinance 2012 Venue: Toronto Tel: 1-866-342-4933 Fax: 1-866-342-4934 Email: kvanvogt@biofinance.ca Web: www.biofinance.ca

JUNE 2012 June 2-4 Labcon 2012 Venue: Gatineau, QC Web: www.csmls.org/labcon2012

MARCH 2012 March 11-16 PITTCON 2012 Venue: Orlando, FL Tel: 412-825-3220 Fax: 412-825-3224

June 18-21 BIO 2012 Venue: Boston, MA Web: www.convention.bio.org

COMPANY & ADVERTISER INDEX COMPANY

PAGE

WEBSITE

Aeterna Zentaris Inc................................................................................... 6, 10......................................................................................www.aezsinc.com Air Science................................................................................................... 26....................................................................................www.airscience.com AlbertatBay...............................................................................................................27..........................................................................................www. Albertatbay.com Amorfix Life Sciences.................................................................................... 9........................................................................................ www.amorfix.com Bestwestern Victoria Park Suites..........................................................................27..........................................................................................www.victoriapark.com BioPartnering North America................................................................................31....................................................................................www.techvision.com/bpn BioTalent Canada......................................................................................................5.................................................................................................... www.biotalent.ca Caledon Laboratory Chemicals.............................................................................7...........................................................................................www.caledonlabs.com Canadian Renewable Fuels Association........................................................ 7..................................................................................... www.greenfuels.org CNA Canada...............................................................................................................2.................................................................................................www.cnacanada.ca Conference Board of Canada........................................................................ 7.............................................................................www.conferenceboard.ca Eisai Limited.................................................................................................. 9..............................................................................................www.eisai.com Eppendorf.................................................................................................................32............................................................................................ www.eppendorf.com Helix BioPharma...........................................................................................6,9..........................................................................www.helixbiopharma.com Mettler Toledo............................................................................................. 26............................................................................................... www.mt.com Mississauga...............................................................................................................19............................................................................www.mississauga.ca/business Novadaq Technolgies Inc............................................................................. 10 .....................................................................................www.novadaq.com Performance Plants Inc................................................................................ 10..................................................................... www.performanceplants.com Perkin Elmer................................................................................................ 26................................................................................ www.perkinelmer.com SinEtsu......................................................................................................... 26........................................................................ www.shinetsusilicones.com Thermo Scientific......................................................................................... 26..........................................................................www.thermoscientific.com Valeant Pharmaceuticals International Inc................................................... 10.............................................................................www.valeantcanada.com Verisante Technology Inc............................................................................. 10..................................................................................... www.verisante.com VWR............................................................................................................................15......................................................................................................... www.vwr.com 28 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

THE LAST WORD

By Robert Foldes

WANTED:

A champion for home-grown Canadian biopharma

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

s the often quoted Chinese curse (with unknown origins) goes – “May you live in interesting times” – it is indeed interesting times for the Canadian biopharmaceutical industry. As a sector dominated by companies engaged in drug discovery and development rather than sales and marketing, its lifeblood requires large and regular infusions of cash. To no one’s surprise, raising capital continues to be the biggest challenge facing the industry and many feel that government can play a significant role in the industry’s success (BIOTECanada/PWC Canadian Life Sciences Industry Forecast 2011). In fact, Ernst & Young highlighted a “funding crisis” facing the industry. The Expert Panel on Federal Support to R&D (The Jenkins Report) recently released its recommendations addressing many hurdles that apply to the industry. However, this panel’s recommendations relating to the SR&ED tax credit program, may have negative consequences on many biopharmaceutical companies that rely heavily on outsourcing the majority of R&D expenditures. The SR&ED program is of immense importance to the sector. Efforts to improve access to and predictability of the SR&ED program are applauded but efforts to dismantle or reduce its impact could quite easily deliver a death-blow to an already fragile sector. A recent Mowat Centre Report by Tijs Creutzberg also released several similar messages as the Jenkins Report in improving Canada’s innovation ROI: reduce tax incentives and increase direct support to companies; simplify access to federal and provincial support programs and reduce bureaucratic infrastructure. In Ontario, the newly re-elected Liberal government has proposed a 35 per cent start-up tax credit to boost investment. However, one thing is clear, the Canadian biopharmaceutical industry needs immediate and targeted action from both levels of government. Its challenges are far more acute and severe than other sectors of the knowledge economy. Given the current turbulence of global financial markets, biopharmaceutical companies are the “low man on the totem pole” and public financings of non-revenue generating companies have essentially disappeared from a CFO’s arsenal. For a host of reasons, venture capital investment in this sector has also retreated. Again due to the trickledown effect of global financial uncertainty, investors in venture capital funds are not currently favouring the biopharmaceutical sector due to long product development timeframes, large investments required, increased regulatory risks, and poor returns in previous venture capital funds. As a result, many venture capital funds have faced

an impossible environment to raise new funds. Some have given up. For those that are still investing (generally nonCanadian funds), desired exits are quite short due to the maturity of the funds - in some cases as little as 3 years. As a result, in the current environment, venture capital – no longer characterized as patient capital – requires validated drug candidates very close to starting human clinical trials or ideally with early clinical data. (A little more than 10 years ago, a drug discovery company with a pending patent application claiming the use of a novel gene would find little trouble in attracting financing.) A new business model has started to emerge in the venture capital community – that of project based financing. This model generally takes the “company” out of the “virtual company” model. In the latter case, a team of experienced executives would be responsible for project management with most R&D activities outsourced to CROs. In the new model being implemented by a few groups (so far), the venture capital team itself is responsible for project management of drug candidates that are in-licensed or acquired and generally advanced to the point of attracting a pharmaceutical company partner. That stage could be attained once human proof-of-principle is obtained, or earlier. The idea is to channel all investment to R&D rather than building overhead in a company. However, underneath the hype, one would assume that the venture capital group would still need to build overhead in-house. DECEMBER 2011 / JANUARY 2012 BIOTECHNOLOGY FOCUS 29

THE LAST WORD Very few existing venture capital teams have the requisite experience and motivation to navigate the intricacies of early stage drug development. One needs to recognize that managing development of an Alzheimer’s disease drug is not the same as for a cancer drug and requires deep experience and specific expertise. Hunger and perseverance is also a key factor in the equation which may account for many abandoned drugs that later re-emerge under a new team to great commercial success. As far as investments go, patience and perseverance are not typical characteristics of venture capitalists. The funding gap for a start-up biopharmaceutical company is as wide as it has ever been. This funding gap now refers to the financing required to advance a new therapeutic (generally from a hit molecule discovered in an academic institution) to the point of being able to file regulatory applications to initiate clinical trials. On average, $2 to $3 million is required for this purpose per drug

“The sustainability of the biopharma sector depends on a continual flow of new startups to both feed Big Pharma’s pipelines and to create the next generation of emerging mid-cap companies…(and)…we aren’t starting enough new companies…” – Bruce Booth candidate. A novel oncology drug candidate is probably the cheapest to develop due to a reduced requirement for several safety studies. Prior to company formation or securing matching funds, there are no individual government programs that can come close to filling this financing need. But the landscape is not barren for Canadian researchers. There is early stage proof-of-principle funding available from the CIHR. In addition, the Canadian government has continued to build sizeable infrastructure through the Centres of Excellence program. A staggering $451 million has been awarded through this program to current initiatives in health and life sciences. Several of these Centres of Excellence are able to deploy resources to de-risk novel therapeutics originating from academia. However, to an outside observer, it seems that many of these Centres favour channeling opportunities to large pharmaceutical companies rather than engaging entrepreneurs and creating new companies. In select situations provincial programs to address this funding gap have also been established. Once a company is formed and matching funds are available, other government programs can be accessed. As highlighted in the Jenkins Report, navigating the full breadth of government programs available in Canada for any entrepreneur is a time-consuming and daunting task and simplification is urgently needed. Given the current prevailing response to economic realities by focusing on out-licensing drug candidates to multi-national pharmaceutical companies and bypassing the process of company creation or supporting 30 BIOTECHNOLOGY FOCUS DECEMBER 2011 / JANUARY 2012

company growth, is the dream of building a sustainable biopharmaceutical industry in Canada dead ? As Bruce Booth (Partner, Atlas Venture) wrote in his Sept 9th blog (lifescivc.com) on Our Shrinking Biopharma Ecosystem: “The sustainability of the biopharma sector depends on a continual flow of new startups to both feed Big Pharma’s pipelines and to create the next generation of emerging mid-cap companies…(and)…we aren’t starting enough new companies…”. Imagine that if this is the situation in the U.S., our policies in Canada have further exacerbated the problem. Given that we all depend on the biopharmaceutical sector to deliver new therapeutic innovations, and that this sector represents only 25 per cent of BIOTECanada’s membership, perhaps we need a dedicated voice to represent the interests of home-grown Canadian biopharma companies. We also need to fill the gap left by the demise of labour sponsored investment funds. Some measures to strengthen an ecosystem that can boost start-up activity include: 1. Universities need to recognize the efforts of researchers in patenting their discoveries through the tenure process. 2. Universities and granting agencies should devote a suitable percentage of research grants/budgets to the protection of intellectual property. 3. Universities should engage entrepreneurs to help manage the commercialization of inventions. 4. The federal and provincial governments can create start-up loans with no interest and generous repayment provisions for experienced entrepreneurs. 5. Universities should engage alumni towards the establishment of seed funds for university-originated inventions. These funds would only support proof-ofprinciple research and preclinical development. 6. The federal and provincial governments should support professionally-managed university seed funds through direct investment and tax incentives for other investors. The above is not unique to the biopharma sector and can only help to rebuild the start-up pipeline. True sustainability of the biopharmaceutical sector will depend on learning from the past and establishing new models, new approaches, and new paradigms. (See Bruce Booth’s October 12th blog for interesting perspectives.) Perhaps we need to learn how to consistently hit singles and load the bases before aiming for the bleachers. Our primary focus needs to be on generating investor returns in a relatively short period of time, say 5 years from seed investment. Happy investors will snowball and will direct more risk capital for the sector. Cognovie Inc. is engaged in life science business development consulting and start-up company formation. It readily identifies with Bruce Booth’s tagline - “a biotech optimist fighting gravity”.

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

10th Annual BioPartnering North America™

Growing Life Science Business in the Pacific Rim

www.techvision.com/bpn

10th Annual BioPartnering North America™ Vancouver Convention Centre | Vancouver, BC, Canada 26-28 February 2012 BioPartnering North America (BPN) focuses on the Pacific Rim because this is where a lot of life science business will be taking place in the years to come. We plan to build on close ties with industry leaders in the Pacific Rim to create a unique opportunity for the U.S., Canada, and Europe to meet leading life science companies from Asia. BPN represents a cutting-edge solution to the major problem faced by busy executives: “who should I meet with today?” Business opportunities and strategic partnerships exist for pharma, investors, and emerging biotech companies – this is what BPN helps life science companies do. BPN is a focused event for serious dealmakers! Visit the conference website to find out what makes BPN different from other events.

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Biotechnology Focus April 2011

Articles inside

CAN CANADA CLEAN UP IN CLEAN-TECH?

THE LAST WORD

STEREOTACTIC BODY RADIATION THERAPY

BIOSIMILAR BATTLEGROUNDS