Biotechnology Focus February 2010

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INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

FEBRUARY 2010 VOLUME 13, NUMBER 2

TARGETED CANCER THERAPY Oncology Clinical Development: Challenges and Opportunities

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GOVERNMENT INITIATIVE Promotes R&D Partnerships

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Government initiative promotes R&D partnerships

FEATURES

FEBRUARY 2010 – VOLUME 13 – NUMBER 2

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COVER STORy

Clinical development challenges for cancer therapies

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FLUORESCENCE IMAGING and Automated Microscopy for Cancer Management in the Developed and Developing World (By SCalum MacAulay, Martial Guillaud and Pierre Lane)

ONCOLOGY CLINICAL DEVELOPMEN Challenges and opportunities in the Phase 1 setting (By Denise Deakin and Dr. Luc Daigneault)

DEPARTMENTS 6

RESEARCH NEWS

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BUSINESS CORNER

18 University spin out transforms CNS drug discovery

IN EVERy ISSUE

26 PRODUCT NEWS 28 CALENDAR OF EVENTS

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30 THE LAST WORD

22 R&D NEWS

Synchrotron researcher wins prestigious Canadian chemistry award www.bioscienceworld.ca

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INNOVATOR Jeff Coull, CEO and president of Chlorion Pharma (By Shawn Lawrence)

ACROSS CANADA A new strategy to promote increased R&D collaboration (By Quinn Damery)

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Final

PUBLISHER’S NOTE PUBLISHER/ EDITOR-IN-CHIEF

Shawn Lawrence

CONTRIBUTING WRITERS

Calum MacAulay

Martial Guillaud

Pierre Lane

Denise Deakin

Quinn Damery

National Account Manager GRAPHIC DESIGNER

The largest celebration of

science in Canada

O

n October 28th-30th, the world’s most celebrated scientific superstars gathered in Toronto to mark the 50th anniversary of the Canada Gairdner Awards. For the auspicious occasion, the Gairdner Foundation planned the biggest celebration in its history. In all, more than 60 past winners, including 22 Nobel Laureates, visited the University of Toronto to participate in a series of free lectures - open to both academics and the public. Students, teachers, scientists and other members of the scientific community packed the lecture halls and labs clustered around the campus leaving little or no standing room. Many attendees were even forced to listen to the some 35 lectures from outside the lecture room doors. Despite the crowded conditions, attendees were treated to a remarkable lineup of scientists, both Canadian and world renowned. Established in the 1950’s by Ontario stockbroker James Arthur Gairdner, the Gairdner’s have undergone an evolution from one of the best kept secrets to becoming more main stream. This year the Canada Gairdner Awards were handed out to seven recipients from a range of medical fields and included: Dr. Shinya Yamanaka, Dr. Peter Walter, Dr. Kazutoshi Mori, Dr. Lucy Shapiro, Dr. Richard Losick and Dr. David Sackett. There was also the inaugural presentation of a new category of award-the Canada Gairdner Global Health Award to Nubia Munoz. Munoz was honoured for her discovery of two strains of human papilloma virus, a development that led directly to the breakthrough vaccine protecting against HPV. Recipients were also given a larger cash award from past years, with each receiving $100,000 as opposed to the previous $30,000 prizes. The increase was made possible by a $20-million donation from the federal government. Every indication from the massive turnout is that Canadian’s do indeed care about their science. With a track record of identifying significant work early; the Gairdner’s have a reputation of respect and prestige within the scientific community. Of the 298 individuals who have received the award, more than 25 per cent have gone on to win the worlds’ top medical research prize, the Nobel Prize. One can’t deny the role that both the Gairdner Foundation and these awards have played in enhancing Canada’s international scientific reputation. At the same time, they continue to provide a benchmark for Canada’s leading scientists, driving the culture of scientific excellence in Canada.

Terri Pavelic

STAFF WRITER

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R & D NEWS

Tsun-Kong (T.K.) Sham

Synchrotron researcher wins prestigious Canadian chemistry award

Professor Tsun-Kong (T.K.) Sham, Canada Research chair in Materials and Synchrotron Radiation at The University of Western Ontario (Western) and a driving force behind the development of the Canadian Light Source (CLS), is the recipient of the Canadian Society for Chemistry John C. Polanyi Award. Sham is being recognized for his outstanding contributions to the field of physical chemistry, using synchrotron light and other advanced spectroscopic techniques to study the chemical structure of nanomaterials. “It feels good to receive one of the most prestigious awards given out by the Soci-

ety,” said Sham. “The whole synchrotron community also deserves a lot of credit, including the scientific staff at the CLS, collaborators, my students and post-docs over the years. Their contributions really make this work possible.” Sham is one of the founders of synchrotron science in Canada, having worked with other Western researchers at the Canadian Synchrotron Research Facility beamlines at the Synchrotron Radiation Center in Madison, Wisconsin. He took on a leadership role in the development of the CLS, is principal investigator on three of the beamlines at Canada’s synchrotron, and has served on the facility’s Board of Directors. “Everyone at the CLS is thrilled that T.K. is being recognized with the Polanyi award,” says Thomas Ellis, director of Research at the CLS. “His energy and enthusiasm are inspirational. He’s a key reason for our success.” Nanomaterials – substances whose sizes are reckoned in billionths of a metre (a sheet of paper is about 100 000 nanometres thick) – make nanotechnology possible. Sham and his research group use the CLS to study the structure of nanomaterials to understand how they work in order to create nanotech devices that can lead to smaller, faster computers, superefficient lighting, better catalysts and lighter, stronger materials. The Polanyi Award will be presented to Sham during the Canadian Society for Chemistry’s annual meeting, May 29 to June 2 in Toronto.

Feds invest in clean energy projects Through the Government of Canada’s Economic Action Plan, an investment in renewable energy projects was announced, which will create jobs, improve the environment and stimulate the economy. The Honourable Lisa Raitt, Canada’s Minister of Natural Resources, announced support for 19 projects under the Clean Energy Fund. Funding of up to $146 million will support the demonstration of renewable and clean energy across the country, including in-

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tegrated community energy solutions, smart grid technology, and renewable applications with solar, wind, tidal and geothermal energy. “Investments in clean energy technologies are a key part of our approach to reducing greenhouse gas emissions and improving the environment,” said Minister Raitt. “Canada’s Economic Action Plan is investing in 19 innovative projects that will help bring Canada to the forefront of clean energy technology, while creating high-quality jobs for Canadians.”

Clinical Trials & Patents n Protox Therapeutics Inc. (Vancouver, BC) announces positive top-line results from its double-blinded placebo controlled Phase 2b study of PRX302 (study name: TRIUMPH) in patients with moderate to severe benign prostatic hyperplasia (BPH). The study achieved its primary clinical endpoint of a statistically significant improvement in International Prostate Symptom Score (IPSS) for patients treated with PRX302 versus subjects receiving placebo (p=0.0238, ANCOVA), scores greater than or equal to 15, a maximum urinary flow rate (Qmax) of less than 12 milliliters per second and prostate volume between 30 and 100 millilitres. Each subject was treated with either PRX302 (3 microgram/mL) or placebo at a volume equivalent to 20 percent of the total prostate volume via a single ultrasound guided injection into each lobe of the prostate. The trial’s primary clinical endpoint of the study was to determine the efficacy of PRX302, as demonstrated at 90 days post-treatment, by a statistically significant improvement in IPSS from baseline when compared to placebo. Of the 73 per protocol efficacy evaluable subjects, 52 received PRX302 and 21 received placebo. The PRX302 arm showed an average IPSS improvement at 90 days of 9.1 (+/- 5.9) points versus an average IPSS improvement of 5.8 (+/- 5.4) points for the placebo arm, a statistically significant improvement of 3.3 points (p=0.0238, ANCOVA). Baseline average IPSS for the PRX302 and placebo groups were 23.5 and 22.9 points, respectively. No significant safety issues were identified in this study. There were no drug related serious adverse events or Grade 3 or greater adverse events reported in the study. PRX302 related adverse events were mild to moderate, transient in nature (resolved within days) and localized to the urinary tract. In addition, no sexual dysfunction was reported in any of the subjects. n Theratechnologies (Montréal, QC) announces that the Brazil Patent and Trademark Office has issued patent Number 9608799-4 entitled “Chimeric fatty body-pro-GRF analog with increased biological potency and pharmaceutical formulation” for its lead-compound, tesamorelin. The granting of this patent provides protection in Brazil until December 2019. The company also announced that the U.S. Food and Drug Administration (FDA) has confirmed that the Endocrinologic and Metabolic Drugs Advisory Committee will meet to review the company’s New Drug Application (“NDA”) for tesamorelin on Wednesday, February 24, 2010.


R & D NEWS Genomic surveillance of pandemic H1N1

www.caledonlabs.com

The BC Centre for Disease Control has launched an influenza genome sequencing project to better understand how the pandemic H1N1 flu virus has evolved in British Columbia, and may continue to evolve in the coming months. The project capitalizes on BC’s expertise and capacity in genome sequencing to generate hundreds of complete genomes from circulating influenza viruses collected in BC during the H1N1 pandemic, as well as during and after the Olympics. By comparing the evolution of BC’s influenza virus to that of viruses sequenced in other regions, researchers hope to learn how a mass gathering such as the Olympics can impact the virus’ genetic sequence. The project will also allow researchers to track the geographic origins of the H1N1 virus that entered BC in 2009. “We know from earlier studies that one of the most important drivers of an influenza virus’ evolution is the mixing of different lineages of virus from around the world,” explains Dr. Robert Brunham, Provincial executive director of the BC Centre for Disease Control. “While we are not expecting a third wave of H1N1 in BC, we will have over 250,000 visitors in Vancouver in February, which may impact influenza virus evolution.” Although researchers predict that ex-

posure to influenza viruses from different countries will lead to changes in the H1N1 virus’ genetic sequence, these changes are unlikely to change the severity of disease due to the H1N1 virus. “The data uncovered from this project will enable BC to track how the virus moved through the population - information that can assist public health officials in understanding the virus and preparing for future outbreaks,” explains Dr. Perry Kendall, British Columbia’s Provincial Health officer. Large-scale genome projects such as this have only become common in the last five years, as sequencing technologies have improved and become faster and more cost-

efficient. “This is the first time since this technology has matured that both a pandemic and an Olympics have occurred together,” says Dr. Alan Winter, president and CEO of Genome BC. “The timing provides a very significant opportunity to study how a virus evolves when it is meeting and mixing with viruses from around the world.” The project is jointly funded by the BC Centre for Disease Control, Genome British Columbia and Genome Canada. Research is being conducted at both the BCCDC Public Health Microbiology & Reference Laboratory and Canada’s Michael Smith Genome Sciences Centre.

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R & D NEWS Island Labs announces Health Canada approval for Stemcelex and appoints Lorne Meikle as Board chair

Lorne Meikle

Island Labs, a company developing natural dermatological products, has become the first company in Health Canada’s history to receive Natural Health Product (NHP) approval. In the U.S. and Canada alone there are over 50 million men and women experiencing premature thinning or hair loss. Stemcelex is a patented (PCT filed) product that has demonstrated hair growth for men and women on all areas of the scalp, including areas affected by androgenic alopecia (pattern baldness). Stemcelex naturally stimulates the population of stem cells within the hair follicle. Over thirty years in development, the product is safe and has shown to produce no adverse side effects. The company also announced that Lorne Meikle has been appointed board chair at Island Labs. He will direct the global licensing and commercialization of Stemcelex. Meikle was a member of senior management teams at industry leaders: Glaxo Canada, Smith Kline and French, OrthoMcNeil and Connaught Laboratories. Having served as CEO for nine biotechnology companies, Meikle is currently president and CEO of Management Dynamics Ltd., a biotechnology and water resources firm; LOB Ordeins Inc., a human therapeutics delivery company and CEO of Neuroimage Inc. He is also chairman and director of Quest PharmaTech Inc. and president of The Biotechnology Initiative.

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Sunnybrook cardiac surgery founder receives Order of Canada

Dr. Bernard S. Goldman Dr. Bernard S. Goldman has been appointed to the Order of Canada for his contributions to the field of cardiac surgery and cardiac care. Dr. Goldman founded the cardiac surgery program at Sunnybrook’s Schulich Heart Centre, which has become one of the country’s leading research and teaching centres for surgical interventions to treat cardiovascular disease. A renowned clinician, researcher and educator he has also been a mentor for countless professionals in the field, pioneering new approaches to aortic valve replace-

ment, coronary artery bypass grafting and cardiac pacing. “Dr. Goldman is a true innovator and leader in his field and Sunnybrook is fortunate to have him as a member of our team,” said Dr. Barry McLellan, president and CEO of Sunnybrook Health Sciences Centre. “This is a well deserved honour that complements what has been an outstanding career.” Dr. Goldman came to Sunnybrook in 1989 and served as head of the Division of Cardiac Surgery from 1989 to 1999 and as Surgeon in chief of Sunnybrook from 1999 to 2003. In addition to his role as Cardiac Surgeon, Dr. Goldman is a professor of Surgery at the University of Toronto, editor of the Journal of Cardiac Surgery and chairman of Save a Child’s Heart Canada, providing heart surgery to children from underprivileged countries at no cost. He has also led numerous research efforts to improve the care of cardiovascular surgery patients, has authored hundreds of peer reviewed articles, contributed chapters to medical text books and has recently published the second edition of Heart Surgery in Canada: Memoirs, Anecdotes, History and Perspectives. In honour of his contributions, Sunnybrook has established the Dr. Bernard S. Goldman chair in Cardiovascular Surgery. The chair supports initiatives in teaching, innovation and clinical evaluation.

FDA grants orphan drug status to Allon’s davunetide for brain disease The United States Food and Drug Administration (FDA) has granted Orphan Drug Designation to the Allon Therapeutics Inc. lead neuroprotective drug candidate davunetide for the treatment of Progressive Supranuclear Palsy (PSP), a rapidly-progressing and fatal degenerative brain disease. Gordon McCauley, president and CEO of Allon, said Orphan Drug Designation brings additional commercial benefits to the company’s program to develop davunetide to become the first approved treatment for a disease often mis-diagnosed as Parkinson’s or Alzheimer’s disease. “PSP is devastating for thousands of middle-age patients and their families,” said McCauley. “Meeting the desperate need for a treatment is a significant business opportunity for Allon made more attractive by the FDA’s Orphan Drug Designation for davunetide.” McCauley commented that Allon has demonstrated a strong scientific and clinical rationale for the potential efficacy of

davunetide in PSP adding that davunetide’s potential as a treatment for PSP was confirmed in both animal studies and Phase II human clinical trials with patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s. “Our research has shown that davunetide reduced tau impairment and preserved memory in mice bred to replicate Alzheimer’s or PSP tau pathology. In addition, our Phase II clinical trials have shown that davunetide can also improve memory function in aMCI patients.” Allon’s clinical program in this area is expected to begin shortly with a pilot trial treating a small number of patients with tau impairments, including PSP. This trial will help validate the trial design and prepare for a larger Phase II clinical trial that the Company intends to initiate in 2010. Trial investigators are among the leading experts in the field, including Drs. Bruce Miller and Adam Boxer of the Memory and Aging Center of the University of California, San Francisco.


BUSINESS CORNER Therapure Biopharma and Stellar Pharmaceuticals announce contract Therapure Biopharma Inc. and Stellar Pharmaceuticals Inc. have signed an agreement under which Therapure will provide fill/finish services for pre-filled syringes of Stellar’s natural viscosupplement, NeoVisc®. Under the terms of the agreement, Therapure will formulate and fill NeoVisc® into sterile syringes at its licensed facility, using equipment specially designed for this process. NeoVisc® is a viscosupplement that, when injected into the synovial space of affected joints, offers osteoarthritis patients a drug-free method to treat the

pain associated with their condition. It uses a natural, linear hyaluronan derived from a fermentation process, unlike competitive viscosupplements that use an altered, cross-linked hyaluronan. The primary benefit of using linear versus cross-linked hyaluronans is that the former is believed to be less likely to cause sensitivities or allergic reactions than the latter; Stellar is currently the only company in Canada to provide a natural linear molecular hyaluronate product in both a single-dose and three-dose injectable format.

Canadian biotech’s keep FDA Busy; three approvals possible in Q1 With three Canadian biotechs seeking U.S. drug approvals this year - and all decision dates crowded in the first quarter - the tone for Canada’s health care sector in 2010 could be set according to the Wall Street Journal. First up on Feb. 6 is IntelGenx Technology Corp.’s CPI-300, a high-strength formulation of antidepressant Wellbutin XL, expected to be followed by Labopharm Inc.’s (DDSS) once-daily formulation of antidepressant Trazodone on Feb. 11. Finally, and perhaps most important, is

Theratechnologies Inc.’s Tesamorelin on March 29. The drug, a treatment for excess body fat in HIV patients, is the only new chemical entity of the trio, and will be the subject of an FDA advisory meeting Feb. 24. The decision dates aren’t set in stone, as the FDA has been known to be early and late. Wayne Schnarr, a health-care consultant at Equicom Group, a unit of TMX Group Inc. said the closeness of the approval dates could shine a light on the sector after it was largely ignored last year. Last year’s major disappointments in-

cluded failed Phase III trials by BioMS Medical Corp. and Aeterna Zentaris Inc., as well as the halting of high-dose trials for Transition Therapeutics Inc.’s Alzheimer’s disease drug. On the plus side, Cardiome Pharma Corp. signed a big partnership deal with Merck & Co. and Nuvo Research Inc. won FDA approval of its topical drug Pennsaid. Other companies to watch with Phase III data on tap this year include WEX Pharmaceuticals Inc., Bioniche Life Sciences Inc., Aeterna, and YM BioSciences Inc.

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BUSINESS CORNER ProQuest Investments acquires common shares of BioSyntech, Inc. ProQuest Investments III, L.P., a U.S.-based private venture capital fund, announces that, upon BioSyntech, Inc. exercising its option to issue 8,265,921 common shares to its debenture holders in payment of the $739,800 of interest payable on December 31, 2009 on the $12,330,000 principal amount outstanding Subordinated Secured Convertible Debenture Series issued in 2008, convertible (at a price of $0.20 per share) into common shares (the “2008

Caprion Proteomics acquires biomarker unit from PPD Caprion Proteomics Inc. has acquired from PPD, Inc. the shares and assets of PPD Biomarker Discovery Sciences, LLC, PPD’s proteomics-based biomarker services division based in Menlo Park, Calif. The acquisition, which closed on December 31, 2009, further strengthens Caprion’s market leadership position in the area of proteomics biomarker services and will also broaden its client portfolio and revenue base. Financial terms of the acquisition were not disclosed. Caprion will perform existing contractual obligations required as part of this

acquisition from both Caprion’s facilities in Montreal and from a new facility in Menlo Park that will operate under the name Caprion Proteomics, U.S., LLC. “We are very pleased to add the solid scientific capabilities, experience and customer relationships of PPD’s biomarker unit to Caprion’s rapidly growing biomarker services business,” said Martin LeBlanc, president and CEO of Caprion. “By acquiring this business, we will expand our capacity and be able to better meet the growing biomarker needs of our current and future clients.”

Debentures”), it has received a total of 2,011,173 common shares of BioSyntech in payment of the $180,000 interest payable on $3,000,000 principal amount of 2008 Debentures held by ProQuest. As a result of this issuance and as of the date hereof, ProQuest holds an equivalent of 18,430,172 common shares representing approximately 16.09% of the total issued and outstanding common shares of BioSyntech on a non-diluted basis, 18,750,421 common share purchase warrants, $3,000,000 principal amount of 2008 Debentures, convertible (at a price of $0.20 per share) into 15,000,000 common shares, $280,000 principal amount of a Subordinated Secured Convertible Debenture Series 2009-1, convertible (at a price of $0.11 per share) into 2,545,455 common shares, and $956,310 principal amount of a Subordinated Secured Convertible Debenture Series 2009-2, convertible (at a price of $0.11 per share) into 8,693,727 common shares. In the event that the debentures held are fully converted and that all of the warrants held are fully exercised by ProQuest and that no other convertible securities are converted or exercised, these holdings would represent approximately 39.76% of the total issued and outstanding common shares of BioSyntech as at December 31, 2009.

Dealmakers Therapure Biopharma Inc. (Mississauga, ON) has signed a partnership agreement with Microbix Biosystems Inc. (Mississauga, ON) to manufacture and market water-based products to the pharmaceutical, biotechnology and other industries. Under terms of the agreement, Microbix will maintain the sales and marketing functions for the water-based program, while Therapure will manage manufacturing and product development operations. The products will remain under the Microbix brand. Further financial details of the transaction were not made public. The immediate result of the Microbix-Therapure agreement will be the launch of Microbix 22™, a new 22% alcohol and water-for-injection (WFI) pre-mixed used for chromatography column storage. Mixing concentrated alcohol with water can be dangerous and many customers would rather purchase the product premixed and avoid the risks. Additionally, the partnership will be able to manufacture custom buffers and media to recipes provided by customers.

n

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Patheon (Research Triangle Park, NC) an-

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nounces it has signed two five-year manufacturing agreements with Sanofi-Aventis. The agreements, for products manufactured in Patheon’s Swindon and Bourgoin facilities, extend the company’s longstanding partnership with Sanofi-Aventis to provide outsourced manufacturing services. n Miraculins Inc. (Winnipeg, MB), a medical diagnostic company has entered into a partnership with Inverness Medical Innovations, Inc. (Waltham, MA), to advance and commercialize Miraculins’ preeclampsia technology. Miraculins’ preeclampsia technology is based on a suite of 35 novel biomarkers involved in the development of the placenta and the biology implicated in the development of preeclampsia, a debilitating and potentially fatal complication of pregnancy. The goal of the partnership is to commercialize Miraculins’ biomarkers for worldwide distribution. In addition to its research and development commitment, Inverness will pay a non refundable fee to Miraculins for the exclusive option to license and commercialize any biomarkers of interest from the program.

Miraculins retains certain commercial rights to pursue complementary commercial strategies for the markers and receives from Inverness a secure supply of reagents and certain rights to intellectual property related to the biomarker endoglin. Inverness can exercise its option to license at any time during the term of the Collaborative Research and Option Agreement. Upon exercise of the option, Miraculins will receive additional fees, developmental and commercial milestone payments, and royalties on sales. In connection with this partnership, Miraculins and Mount Sinai Hospital have agreed to certain amendments to the royalty and fee structure of their license agreement originally announced on October 15, 2008. In consideration for the amendments, Miraculins will issue 250,000 common shares from treasury to MSH immediately upon the occurrence of Inverness’ exercising its option to license under the recently announced Collaborative Research and Option Agreement between Miraculins and Inverness. The common shares are subject to a standard four-month and one day resale restriction.


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By Calum MacAulay, Martial Guillaud and Pierre Lane

CANCER

Fluorescence

Imaging and Automated Microscopy for Cancer Management in the Developed and Developing World

Cancer is a common, tragic and expensive disease. While more than 1/3 of the population of North American will be diagnosed with cancer at some time in their lives, and the cost of cancer in the US exceeded $219 billion in 20081, the situation is even worse in the developing world where even less resources are available and the human costs of cancer can be even higher. Most cancers arise from precancerous lesions, and effective detection and removal of precancerous tissue may be the best, most cost-effective means to improve cancer survival and reduce cancer incidence. Early detection of cancer dramatically improves survival; when detected late, treatment is less effective, has greater morbidity, and is more expensive. One of the greatest success stories in cancer management is based upon early cancer detection and is that of cervical cancer screening. Cervical cancer screening is based upon the visual analysis of cytological samples (cells removed by brushing or scrapping and deposited on a slide) to identify patients requiring observation of the cervix using a magnified view (colposcopy). Areas suspect for precancerous or cancerous lesions are biopsied and if pathologically confirmed treatment is applied. Done effectively on a population basis this can reduce cervical cancer incidence and mortality by a factor of 42. Any drug with these characteristics would be considered to be an almost un-

12 BIOTECHNOLOGY FOCUS FEBRUARY 2010

believable blockbuster. While such screening programs have been widely implemented in the developed world, they are not available in much of the developing world due to infrastructure and training costs of such programs. Thus while cervical cancer is not a large killer in the developed world in the developing world it is one of the most common forms of cancer in women and a leading cancer killer3. There have been many efforts to develop clinical systems for the automated or semi- automated interpretation of cervical cytology, while most were technically successful wide spread adoption of these technologies has not occurred in the developed world where they must compete with existing conventional screening laboratories. Rapid advances in affordable computational power over the last several decades and improved understanding of the performance requirements needed for an effective cervical cancer screening program have made it possible to construct automated cervical cytology devices which can be effective components of cervical cancer screening programs in the developing world. An example of this is the implementation of the automated quantitative cytology system initially developed in at the BCCA for the cervical cancer screening4. In partnership with a Chinese company this technology has been clinically implemented in economically successful private clinics and public sponsored clinics in China which have screened over 350,000 women to date. Further this approach is undergoing controlled studies to determine its feasibility as part of a publically funded program. In collaboration with colleagues at Rice University, MD Anderson Cancer Center and Drexel University we have also set up two of these automated quantitative cytology systems in Nigeria to assess their


CANCER

Photo by Randy Wong

utility in the developing world for cervical screening. The vast majority of cancers (~85per cent) arise in the epithelium (tissue connected in one way or another to the world outside the body). Most of these tissues are accessible to investigation by optical technologies. Electromagnet radiation in the near visible and visible part of the spectrum (380nm to 700nm) is strongly modified (scattered, absorbed, reemitted) by biological tissue. These strong interactions limit the depth into tissue which light can penetrate, but conversely these strong interactions make light based systems sensitive to the subtle changes associated with the development of pre-cancers in epithelial tissue. This is both a challenge and opportunity for optical based disease detection and delineation technologies. One optically based detection technology currently used clinically is in vivo autofluorescence imaging. Some of the molecules in tissue which absorb light can re-emit the absorbed energy as slightly less energetic light i.e. as fluorescence light. The key molecules involved in tissue fluorescence are part of cellular metabolism (such as FAD and NADH) and make up the stroma immediately underlying the epithelium (elastin and collagen). The growth of pre-cancers in the epithelium alters cellular metabolism and can cause tissue remodeling within the stroma, both effects which are detectable by tissue autofluorescence. The first FDA approved commercial application of tissue autofluorescence was for detection of pre-cancer and cancers in the lung. This light induced fluorescence endoscopy (LIFE) device5 developed at the BCCA was found to be more than six times more sensitive for the detection of pre-cancers at high risk of becoming cancer and preinvasive cancers than conventional white light endoscopy. Almost all endoscope manufactures now produce fluorescence enabled endoscopes. However the high cost of such systems has limited the technologies use in other tissue sites. The cost of this technology has changed radically over the last two decades, while initially such systems were on the order of ~$150,000 (laser illumination and image intensifier based detection systems), technical progress has greatly reduced the cost. For example, direct fluorescence visualization devices using battery powered LEDs for illumination and the eye as the detector for the oral cavity can cost as little as ~$2500. Figure 1 shows a comparison of the size and complexity of this technology originally and currently for lung imaging and oral cavity imaging, along with

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CANCER LIFE

Onco LIFE

Lung: Severe Dysplasia

Lung: CIS

VELscope Oral: Cancer

Identafi 3000 Oral: Severe Dysplasia

Figure 1. Pictures of various clinical fluorescence systems used to image the lung and the oral cavity and example images beneath. The far left system is the original LIFE system developed in the late 80s, consisting of a 442nm laser, intensified camera system and computer console and video recorder and printer. The reddish brown areas in the lower autofluorescence images indicate the areas of abnormality, the green areas indicate normal tissue except in the right most fluorescence image in which normal tissue is blue. The near left system is the current Onco LIFE system which uses a filtered arc lamp as its light source and a small sensitive CCD camera, note the large reduction in system size. The reddish brown area in the lower image is the area of carcinoma in situ (CIS). The near right system is the VELscope system used for direct fluorescence visualization of the oral cavity, the illumination is a filtered arc lamp and the detector is the observer’s eye looking through the ocular of the headpiece (replaced in this example by a digital camera to acquire a picture). The reddish area is an example of a cancer not visible under white light imaging. The far right system is the Identafi 3000 system used for direct fluorescence visualization of the oral cavity. Battery powered LEDs are used for illumination and the observers eyes viewing through a coloured visor are the detectors. The reddish area is an example of a severe dysplasia.

examples of the types of images the various devices produce. The latest commercially available fluorescence visualization (FV) devices for use in the oral cavity have shown the ability to not only enable the detection of clinically occult lesions but have demonstrated improved determination of surgical fields6 which has changed clinical practice in BC. Pilot data from the use of FV to establish the surgical field suggests this approach can greatly reduce local recurrence rates for surgically resected oral cancer (from 25 to 30 per cent to below two per cent)7. The cost of current in vivo fluorescence imaging systems is sufficiently low and the systems have very little infrastructure requirements being LED or flash based with digital point and shoot cameras, all battery powered, that they could be used in the developing world. In fact such versions are currently be evaluated for oral cancer and cervical cancer management in the developing world (India, Nigeria) by several research groups. At a time when the global incidence and mortality of cancer is rapidly increasing8 there is an urgent need for effective and affordable tools to facilitate early detection and effective management of pre-cancer not only in the developed world but also in the developing world.

References 1. Society AC: Cancer Facts & Figures 2008. Atlanta: American Cancer Society; 2008. 2. Anderson G, Boyes D, Benedet J, Le Riche J, Matisic J, Suen K, Worth 14 BIOTECHNOLOGY FOCUS FEBRUARY 2010

3. 4.

5.

6.

7.

8.

A, Millner A, and Bennett O. Organisation and results of the cervical cytology screening programme in British Columbia, 1955-85. Br Med J (Clin Res Ed). 1988 April 2; 296(6627): 975–978. http://whqlibdoc.who.int/publications/2002/9241545720.pdf Anderson G, MacAulay C, Matisic J, Garner D, and Palcic B: The use of an automated image cytometer for screening and quantitative assessment of cervical lesions in the B.C. cervical smear screening programme. Cytopath 8(5):298-312, 1997. Lam S, Kennedy T, Unger M, Miller Y, Gelmont D, Rusch V, Gipe B, Howard D, LeRiche JC, Coldman A, Gazdar AF. Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest 113:696-702. (1998). Poh C, Zhang L, Anderson D, Durham S, Williams P, Priddy R, Berean K, Ng S, Tseng O, MacAulay C and Rosin M: Fluorescence Visualization Detection of Field Alterations in Margins of Oral Cancer Patients. Clinical Cancer Res. 12(22):6716-6722, 2006. Poh C, MacAulay C, Zhang L, Rosin M. Tracing the “at-risk” oral mucosa field with autofluorescence: steps toward clinical impact. Cancer prevention research. 2009;2(5):401-4. Boyle P, Levin B: World Cancer Report 2008 IARC; 2008.

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By Denise Deakin and Luc Daigneault

Oncology

Oncology

Clinical Development Challenges and Opportunites

In The Phase 1 Setting Cancer is a disease of the aging population. According to the Canadian Cancer Society, 43 per cent of new cancer cases and 60 per cent of deaths due to cancer occur among those who are at least 70 years old.1 As Canadian baby boomers continue to age, the percentage of seniors in our society will increase from 13 per cent in 2005 to 23-25 per cent by the year 2031. This shift in demographics will be accompanied by a significant increase in the incidence of cancer. In response to the anticipated growing need for cancer treatments, the bio-pharmaceutical industry has turned much of its attention to the continued development of drugs in this therapeutic area. Approximately, 25 per cent of all compounds being researched are those destined to treat cancer and their clinical development is said to represent in excess of $800,000,000 U.S. per compound.2 The many challenges of oncology drug development are as complex as the disease itself. This article will provide a brief overview of targeted cancer therapy and discuss certain challenges to their development, as they relate to the Phase I clinical development setting. Finally, a unique opportunity will be presented that serves to support the efforts of industry and clinicians alike.

Targeted cancer therapies Targeted cancer therapies are currently being developed to respond to a need for more effective treatments producing fewer side effects. These therapies consist of drugs or other substances that may interfere with certain cell signalling pathways or cell receptors involved in cancer cell division, which in turn, block the growth and progression of cancer. It is thought that these compounds may be more effective than other types of treatment, such as chemotherapy and radiotherapy, and less harmful to normal cells by focusing on molecular and cellular changes that are specific to cancer. Most targeted therapies are either small-molecule drugs, able to penetrate cells and target certain cell pathways, or humanized monoclonal antibodies that target certain receptors at the cell surface.

FEBRUARY 2010 BIOTECHNOLOGY FOCUS 15


Oncology

Clinical Development Challenges Phase I clinical trials in all therapeutic areas serve to profile a research drug’s safety and tolerability. This information leads to establishing the maximum tolerated dose for humans. However, unlike Phase I studies in other therapeutic areas, Phase I oncology trials are conducted in patients as opposed to healthy volunteers, since administering cancer drugs to healthy subjects is considered unethical. Phase I oncology trials are usually reserved for patients who have failed prior treatment therapies and who do not have other viable treatment options. Many early Phase trials combine targeted therapies with chemotherapeutic agents which have greater likelihood of causing adverse side effects. The patient population participating in these trials has a higher risk of experiencing these effects because of their compromised physical status. This makes understanding the source of side effects harder and subsequently, adds to the complexity of establishing a maximum tolerated dose. Although the clinician maintains the ultimate responsibility for assuring patient safety, the company medical representative, who is also a physician, is the one who masters all pre-clinical and clinical data on the compound. Together, they discuss causality related to side effects and the company medical representative then determines if it is safe to escalate the dose within a new cohort. If it is, then a new set of patients is recruited. This type of stepwise dose escalation is typical to Phase I trials. Besides managing dose escalation safety issues, managing the cohorts or patient groups themselves is yet another challenge. Patients are enrolled in groups of three at a specific dose and repeatedly administered the research compound and followed to determine how well the drug is tolerated. Unlike other Phases of clinical research where recruitment may occur as a steady flow of patients, recruitment in Phase I trials is dependent on a “safety” green light. Typically there are anywhere from three to five clinical research sites participating and before an oncologist can recruit a new patient, they must first check to see if additional patients are required at a certain dose level. If not, they must wait for approval from the company medical representative to proceed. Despite the fact fewer patients are needed in phase I 16 BIOTECHNOLOGY FOCUS FEBRUARY 2010

trials, they can take in excess of 18 months to complete due to the step-wise process. Pharmacokinetic blood sampling, which provides valuable insight into how the drug is metabolized, is a critical component of Phase I trials. Patients have to comply with blood draws that are performed at very specific intervals throughout the course of a predetermined period. The health care team must ensure that samples are collected, processed, stored and shipped according to strict guidelines in order to ensure their integrity for analysis. All phases of clinical research call for rigorous processes. However, because little is known about compounds in Phase I development, undetected errors are thought to have graver consequences. Therefore, processes have to be extremely well executed and documented on behalf of the clinical research teams. These systems and their documentation must then be verified and approved by an external source such as the company itself, or a third party such as a Contract Research Organization. The data collected and analysed at this stage determines whether the drug continues to move along the drug development continuum, or whether human and financial resources are reallocated to a more promising compound. Go-NO Go decisions determine the future of any given compound.

Bio-pharmaceutical industry challenges Typically, Go-NO Go decisions are taken by biotechnology companies, as they are the key players in the conduct of early phase clinical research. Most of these companies are currently faced with significant financial constraints and therefore, lack the necessary funding to adequately support their clinical research programs. Those that have successfully accessed capitol have done so through partnerships with Venture capitol groups who represent the primary source of funding to the industry. With oncology clinical drug development attrition rates thought to be fourfold higher in oncology, than in other therapeutic areas, companies are under tremendous pressure to provide investor value through sound financial and drug development management. Their strategy is to focus development efforts on the most promising drug candidates in their pipeline, monitoring closely for the first sign of success or failure. Management teams must demonstrate the ability to rapidly reallocate spending where it is best utilized and therefore, flexibility and adaptability are paramount. Working with limited financial resources means biotechnology companies usually con-

duct business with a small number of permanent employees. Many of the drug development components are outsourced to Contract Research Organizations. With so much at stake, the task of delegating complex clinical activities while maintaining accountability can make for highly stressful circumstances. However, if managed successfully, outsourcing can enhance clinical performance and reduce overall costs. Each company must assess their specific needs before making outsourcing decisions, but frequently, small companies need access to core competencies part of their internal organization and often can benefit from the privileged business relationships third parties may have established.

Opportunities Despite the multiple challenges in the clinical development of oncology compounds, it is clear that finding new and better medicines to treat cancer must remain a priority. Canadian investigators, who are known for their commitment to science and quality work, are highly motivated to participate in early phase, cutting edge clinical research. Theses trials represent an opportunity for them to contribute to the understanding of new compounds in the clinical setting. Several have access to state of the art Phase I units and a team of experts at their side. Scimega Research, a Canadian Oncology Contract Research Organization has developed a concept to help investigators attract a greater number of cutting edge trials to Canada. The initiative, called the Reverse FeasibilityTMProgram brings a nation-wide network of qualified Phase I sites together. For investigators, the network provides their team with enhanced international exposure via Scimega Research’s team, who actively pursues business opportunities with U.S. based biotechnology companies, which represents the largest biotechnology hub in the world. Investigators are given the opportunity to further showcase their team’s expertise and to communicate areas of interest related to clinical research. The ultimate goal is to help clinicians attract studies, for which their site currently lack clinical trial activity. This is a novel and efficient way of placing trials. Traditionally, companies either approach investigators directly or mandate a Contract Research Organization with the task of contacting a list of investigators to discuss a specific trial. The hope is that the proposed study arrives at an opportune time where offer and demand intersect. However, the success rate is variable, and the experience can be time consuming and frustrating for both parties, as companies need to move their timelines along quickly to contain costs. This


also leaves investigators with limited time to devote to fruitless queries, while patients are waiting in the wings. The prospect of circumventing the traditional method or at least minimizing its use is very attractive. Rapidly identifying qualified, interested investigators who clearly have an unmet need is a true value added service for the bio-pharmaceutical industry, who experience delays in more than 90 per cent of their trials due to lengthily budget negotiations, slow IRB approval and poor patient recruitment. Companies know that motivated investigators are highly accountable when it comes to meeting important milestones such as obtaining ethics committee approval, and entering a first patient on study. These investigators are also highly likely to respect their patient enrolment target. The commitment and responsiveness they show has a favourable impact on both the quality and the cost of conducting a trial. Furthermore, when companies uses the “Reverse Feasibility Program” in Canada, they have access to the expertise in oncology clinical trials and the privileged business relationships that the Scimega team has developed over the past 12 years. For Canadian investigators, being part of the program means they reduce time spent reviewing information related to clinical trials that do not represent an opportunity for their site. This valuable time may then be redirected to other issues requiring their attention. The Reverse FeasibilityTMProgram is not a panacea for all the challenges that exist in the complex world of oncology clinical drug development. However, the approach brings together Canadian oncology clinical research professionals in an attempt to positively impact areas of high priority to clinicians and industry, such as advancing quality clinical research and containing costs through greater efficiency and quality.

Oncology Traditional Approach

a) Biotechnology companies contact sites or mandate CRO to do so

b) One or few biopharmaceutical companies contract CRO to identify sites

c) Sponsor/CRO contacts list of sites but identifies one or few interested in new trial

Reverse FeasibilityTM Program

a) Scimega maintains active communication with network sites to identify real-time needs

References 1. Canadian Cancer Society – Canadian Cancer Statistics 2009 2. Health Affairs –Volume 25, number 2 page 420-423 (March-April 2006) 3. Clinical attrition rates – Nature Reviews Drug Discovery 8, 15-16 (January 2009) Dr. Luc Daigneault is Director Scientific Affairs Scimega Research

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b) Scimega maintains active communication with biotechnology companies informing them of real-time needs

c) Scimega matches network sites with biotechnology companies and provides clinical trial management

“Canadian centres are very good collaborators who are willing to provide new ideas for studies. The investigators are commonly known to be practical, and clinically oriented and they will provide great feedback to the Sponsors about the feasibility of the trial, the potential hurdles and difficulties for the development of the drug” Dr. Quincy Chu – oncologist - Cross Cancer Institute, Edmonton, AB. FEBRUARY 2010 BIOTECHNOLOGY FOCUS 17


By Shawn Lawrence

INNOVATOR

Chlorion Pharma

Spinning out A highly contested topic of late in biotech is which business model works best for biotech companies. One model that seems to be generating a lot of debate is the value of university spin-offs or spin-outs. Count Dr. Jeffrey Coull, CEO and president of Chlorion Pharma among those who believe in the merits of such a model. Interestingly enough, Chlorion Pharma is a university spin out company whose primary focus is in neurology and the development of novel classes of therapies to restore the normal functioning neurons and other cells. 18 BIOTECHNOLOGY FOCUS FEBRUARY 2010

Success “I always hear people say it just doesn’t happen anymore, the idea of a successful university spin-out. Often they ask is it even possible to spin-out? I keep saying yeah it is and that more people should be doing it especially here in Canada where there’s lots of great science,” states Coull. He adds that the dynamics of success are still the same in the spin-out model, beginning with having the right vision, the right strategy, assembling the right team and of course, raising the capital needed in a timely manner. “It’s all about marrying good technology with a great managerial team,” he says, adding that the first element to success: the technology, can be easily found in our universities but the latter part, i.e. finding the right team and raising capital, is definitely a little more challenging. “It takes time to put together all these elements to produce a successful spin out, but it is still possible,” he says. Coull speaks from experience, after all while it took close to seven years for him and his two co-founders to get Chlorion to where

it is today , it is now a company backed by good science and an experienced management team. The story of Chlorion begins in 2002 in Quebec City, when Coull along with Drs. Martin Gagnon and Yves De Koninck discovered in a Laval University lab, that in conditions of neuropathic pain, the co-transporter KCC2 was dysfunctional in pain-related neurons in the spinal cord. Specifically, KCC2, which normally pumps chloride out of neurons, was discovered to be not operating at full efficiency allowing chloride to accumulate in the cell, increasing hypersensitivity (see Coull et al., Nature, 2003 and 2005). “Say you have nerve injury in your arm or leg, it sends a signal to your spinal cord, which causes this shift whereby the neuro gate that normally prevents touch related information from being perceived as pain in its normal state, goes to being perceived as pain in the pain centres of the brain after trauma,” he explains. “From the very beginning, we wanted to understand what things contribute to that neuronal gate swinging open.”. In trying to understand why neurons in


INNOVATOR

“It’s all about marrying good technology with a great managerial team. The first element to success: the technology, can be easily found in our universities but the latter part, i.e. finding the right team and raising capital, is definitely a little more challenging.” valve. So you can’t get rid of this chloride anymore, it starts to accumulate inside the neuron and it makes it hyperactive.” Just before publishing these papers, the trio filed three patent applications through Laval University protecting their ability to leverage these discoveries to develop novel drugs. In 2004, Chlorion Pharma, Inc. was officially founded. The next step was trying to sell to investors the promise of the idea, particularly the benefits of identifying compounds that would provide better treatments for neuropathic pain through targeting.

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the spinal cord become hyperactive after nerve injury, Coull, Gagnon and De Koninck made several interesting observations using electrophysiology to measure this change. They found that the reason that touch related input doesn’t activate these neurons is because of an inhibition mediated by this transmitter system called GABAergic. “In a nutshell, a channel opens and chloride rushes into the neuron. The reason it rushes into the neuron is because the level of chloride outside the neuron is so much higher than it is on the inside that it’s like water, its going to go from a region of high concentration to a region of low concentration.” What they also found was a neuron in the spinal cord was responsible for making the decision if it sent a painful signal or not. Specifically they found that two co-transporters, NKCC1 and KCC2 were responsible for maintaining low levels of chloride in the neurons. Moreover, in animal models where there was nerve injury there was reversal of the action of chlorides. “GABAergic opens and chloride was actually leaving the neuron. The key point is when it starts to leave the neuron it causes a lot of hyperactivity, and the cells are no longer regulated. That’s because they’re so hyperactive, they can’t filter out information from a paint brush, for example, on the hand they react anyways and that’s why it’s perceived as pain at the level of the brain. The reason that the level of chloride goes up is because of a dysfunction of this co-transporter, KCC2. You can think of KCC2 as an outlet

FEBRUARY 2010 BIOTECHNOLOGY FOCUS 19


INNOVATOR

“We went out to investors and said we have this interesting IP, patent applications and what we want to do is build some assays, provide throughput screening and see if we can pull out some interesting hits that may have potential utility as novel analgesics. Our therapeutic strategy was to go in hit that dysfunction co-transporter KCC2, turn it on and empty out the chloride, and bring it back to normal.” While the potential was exciting, Chlorion was generating very little interest from the investor community. Rather than giving up on the idea, Coull felt a new approach was needed. While Gagnon continued moving forward with the research, Coull returned to Ontario to take on a job with the life sciences

“It was a great experience as I got the chance to work with fortune 500 pharma companies as well as smaller biotech companies, government and universities. I learned a lot about strategic planning, opportunity evaluation and perhaps most importantly what I needed to do to generate interest in Chlorion.” consulting firm SHI Consulting in order to get some seasoning on the business side of biotech. “It was a great experience as I got the chance to work with fortune 500 pharma companies as well as smaller biotech companies, government and universities. I learned a lot about strategic planning, opportunity evaluation and perhaps most importantly what I needed to do to generate interest in Chlorion. In many ways I think of it as my MBA, jumping right into the corporate side of things, having only had scientific training before that. I think that was very important and informative to me, and beneficial to the company.” At the same time, Dr. Gagnon was making some headway with the research, using his post doc to build assays, and ultimately in 2006, was able to do some high throughput screening in collaboration with the National Research Council in Montreal. In doing so Gagnon pulled out some real interesting hits. “We took those hits and put them into some animal models of pain generating positive results. The whole time all this research was being done, I was not only in consulting but also trying to raise money on the 20 BIOTECHNOLOGY FOCUS FEBRUARY 2010

side. I was knocking on door after door, in Canada and the U.S., to some extent even in Europe,” said Coull. “It was a painstakingly slow process, but every time I had a meeting I was learning something new.” Ultimately, Coull was eventually successful in attracting a few investors from Quebec in the summer of 2007. “At that point we had finished our assays, had done our high throughput screening and sorted out the chemical hits. We had hits, positive animal data, and with that we did a Series A $6 million round and we took that and filled out our team.” Chlorion moved from its Laval University labs into, ironically, a facility across the province in Laval, Quebec (the suburb of Montreal) at the QBIC (Quebec Biotech Innovation Centre). “This is the point where we addressed the need to put together a great scientific and management team. First, we hired a real good director of chemistry, Giorgio Attardo, as well as seven other chemists. We started moving forward with our first chemistry effort, started optimizing one compound to make it better for oral administration, better selectivity and better potency against KCC2.” In the summer of 2008, Chlorion had found its first compound to take into full development and then into humans. Unfortunately, that’s when the company ran into a bit of a clinical problem. “The problem we ran into mostly related to the formulation of the compound. Going into this I had never thought a stupid little problem like the ability to put that drug into a solution or liquid solution could kill a drug. Unfortunately we had to kill that, and start again.” So back to the drawing board the team went feeling confident that they would uncover the right compound, in the meantime the company continued to strengthen its team, hiring Franz Hefti as its chief development officer. “He was an individual with quite the track record in neuroscience as the head of neuroscience at Genetech and at Merck. In addition to all that he had written a book about drug discovery in the central nervous system. Not only did he bring experience to our management team, he also brought in a lot of vigour and a lot of CNS knowledge to our program.” The company went one step further hiring, Irenej Kanicka as its director of pharmacology, and before long, following


INNOVATOR

multi-dimensional screening of hundreds of novel openers, they identified a stronger pre-development candidate referred to as CLP-635. “It’s a compound that is really outstanding not only in the efficacy data we’ve seen but also because of its high oral bioviability. Essentially, if you give the drug by mouth orally, you get 95 per cent of the compound into the blood that you would get if you would inject it directly intravenously into the blood system. That’s really good absorption from the stomach. It also has a great half-life.” The compound has also performed well in comparison to Pfizer’s Gabapentin, one of the leading drugs on the market for neuropathic pain, having less of an affect on motor function. Early indications are that when looking beyond a single dose or long term dosing, it performs better then Gabapentin in terms of tolerability. “That’s the problem with current CNS drugs on the market right now. They have efficacy, but they’re really not well tolerated. Patients have weight gain, because of the sedative properties, they get headaches and all sorts of nasty things to the point they no longer want to take them. They would rather grin and bear their pain. That’s what makes it CLP635 so special. If you look at all the drugs in the pipeline today worldwide, I don’t know if you’d find one that marries tolerability and efficacy as well as our compound does.” This is not the only aspect that makes Chlorion’s compound attractive to potential buyers. “Beyond the compound, the interesting case about targeting KCC2 is that there has been evidence recently showing that it has a role in many different disorders particularly those in the central nervous system. It’s not only things like pain, but also epilepsy, stroke, traumatic brain injuries, and on the medical psychiatric side as well, anxiety, bi-polar, the list goes on. So that makes this really interesting, because if you can find a compound that treats KCC2 for one thing, chances are good that it would be very useful for others.” Even big pharma is starting to pick up on this target. “Merck in their worldwide areas of interest book last year included KCC2 for the first time, and it’s starting to get some traction in other trade journals. People are beginning to wake up to the potential of targeting this.” So where is this compound now? “Well, in the summer we should be in hu-

mans, September is what we’re aiming for. We need to take it through the standard GOP studies and then into Phase 1. We also have a backup compound that has been developed to the same point.” He believes none of this would’ve been possible had he not gone the spin-out route. “That, I think, is what has allowed us to do things so efficiently, not only in terms of time but also in terms of capital. I don’t think any of what we’ve accomplished would’ve been possible if we had outsourced everything. We built our own medicinal capacity, our own bioanaltyical chemistry team and our therapure ad_insights.qxd:Layout 1

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own vivarium. I’d say 90 per cent of the work we did ourselves and now we have a single program, with a top notch team. If we had gone a different route, I think we’d have been hard pressed to deliver the same robust results.”

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By Quinn Damery

ACROSS CANADA

Photos reprinted with permission of Angiotech Pharmaceuticals, Inc. © 2010 Angiotech Pharmaceuticals, Inc.

New Government Initiative promotes

R&D R &D

Partnerships A federal government funding agency has launched a new strategy to promote increased R&D collaboration between Canadian industries and the academic sector. The Natural Sciences and Engineering Research Council of Canada (NSERC), one of the largest sources of public-private R&D partnership grants, unveiled their Strategy for Partnerships and Innovation (SPI) in December 2009. The plan is designed to encourage Canadian businesses to leverage academic research resources and excel with their R&D. It involves new government programs that are focused on establishing initial contact between the two sectors to explore partnership opportunities. NSERC has considerable experience in supporting research partnerships through previously available grant and scholarship programs with investments totaling more than $310 million annually. These successful partnerships have led to NSERC working with over 1,400 Canadian companies every year, including 65 of the top 100 R&D investment firms. Now, NSERC is using SPI to expand on that success by reaching out to small and medium enterprises (SMEs). 22 BIOTECHNOLOGY FOCUS FEBRUARY 2010

“Canada has a great research engine,” says NSERC President Dr. Suzanne Fortier. “We have the people and the resources to make our innovation output excel and be more competitive in a global context.” With nearly 20,000 R&D-performing Canadian companies to tap into, the Council is putting a concerted effort into the new strategy and has set ambitious goals for its achievements. Through SPI, they intend to more than double the number of NSERCsupported partnerships from 1,400 to close to 3,000 by 2014. SPI is the result of a year of consultations with more than 200 representatives from industry. The meetings confirmed that businesses had an overwhelming interest in R&D collaborations with the researchers


ACROSS CANADA and students of Canada’s post-secondary institutions. However, without a clear sense of what partnership opportunities existed or how to connect with the right individuals many companies were reluctant to spend the time and effort establishing contacts that could provide the innovation they desired. In response, NSERC designed SPI to bridge this gap between academic innovators and businesses with the know-how to implement ideas in the marketplace. “Partnerships provide great opportunities for businesses and academics. The expertise, information and resources shared between both parties extends their capabilities. With this strategy, we would like more businesses to experience the success we have seen in NSERC-funded partnerships in the past,” says Fortier. SPI builds on previous NSERC partnership initiatives, such as the Industrial Research Chairs program. This program allows an academic at a university, in collaboration with one or more industry partners, to focus on conducting expert research and training highly qualified personnel in an area of importance to the industrial sector. SPI complements existing initiatives like the Chairs program by providing a greater focus

TAXUS, with its paclitaxel-eluting technology, paralyzes cells to prevent their attraction to the site of injury, regulating scar growth and dramatically reducing the occurrence of restenosis.

on SMEs and new levels of funding that increase to accommodate the opportunities of the partnership. Beginning immediately with the strategy’s launch, NSERC’s five regional offices have been re-oriented with a focus on promoting partnership opportunities between industry and academia. The offices, located in Vancouver, Winnipeg, Mississauga, Montréal and Moncton, are reaching out to businesses in their area. They are learning about specific R&D challenges businesses are struggling with and locating suitable researchers who may be able to partner with companies to find a solution. For an initial meeting between potential partners, the Interaction Grant program will fund up to $5,000 to cover travel and meeting expenses for live discussions to take place. If a meeting shows promise for both parties, the partnership can then apply for an Engage Grant. To qualify, companies must operate from a Canadian base, be engaged in R&D, actively participate in the collaboration and exploit the results within Canada. This program provides up to $25,000 for new research collaborations that identify company-specific, short-term R&D challenges. As with all NSERC programs, the funding sup-

Reply Card #4674 FEBRUARY 2010 BIOTECHNOLOGY FOCUS 23


ACROSS CANADA ports the academic researcher’s direct project costs. Business partners provide input that guides the focus of the research and gain the benefits it produces. For the many companies that do not have their own laboratory, or only limited research facilities, they also gain the benefits of university resources. For some partnerships, this initial collaboration may resolve their present R&D needs but for others it will be just the beginning of an invaluable relationship. Businesses have a choice of subsequent NSERC grant programs to advance their R&D partnership with academic researchers. The Collaborative Research and Development Grants, Strategic Networks Grants and Industrial Research Chair program are cost-sharing initiatives that provide substantial funding that matches cash and in-kind contributions from companies. These amounts can be in excess of $500,000 for multi-year projects. While these initiatives are in place, the five-year SPI plan foresees the implementation of additional initiatives. For instance, one of the actions planned for implementation is the establishment of Technology Access Centres (TAC). TACs will provide locations where businesses can go to form new R&D partnerships, similar to the College Centres for Technology Transfer that are part of Quebec’s CEGEP network. TACs will give businesses access to facilities and personnel on campuses to help with the development of innovations and will likely become valued resources for companies looking to jump hurdles in their R&D. Dr. Helen Burt is the Associate Dean of Research and Graduate Studies in the Faculty of Pharmaceutical Studies at the University of British Columbia. Since 1992, her research lab has collaborated with Vancouver-based Angiotech Pharmaceuticals Inc. on the de-

“Canada has a great research engine. We have the people and the resources to make our innovation output excel and be more competitive in a global context.” — Dr. Suzanne Fortier

sign and development of polymeric drug delivery systems and drug-loaded surgical implants and medical devices. This highly successful partnership is an outstanding example of a multidisciplinary achievement encompassing engineering, biomaterials, drug delivery and clinical research. Angiotech’s primary drug of interest, paclitaxel, inhibits important cellular mechanisms involved in aniogenesis, inflammation and scar formation. It is also the active ingredient in the widely used anti-cancer drug, Taxolreg. When Angiotech researchers realized the potential range of applications for paclitaxel in diseases including rheumatoid arthritis, multiple sclerosis and psoriasis, they knew they had an opportunity to make a valuable contribution to pharmaceuticals. The problem was finding a way to get the water-insoluble compound into and distributed throughout the body. Angiotech turned to Burt, whose expertise in drug delivery could provide the insight they needed to make new treatments for diseases that affect tens of millions of people. “I could see the potential for paclitaxel right away,” says Burt. “There were some technical obstacles in creating the formulations though – we had nothing to guide us.” “Helen is a wonderfully innovative scientist,” says Angiotech’s President and CEO Dr. William Hunter. “We just told her what we wanted and somehow she and her research team made that a reality.” Burt and her team devised a polymer bubble to contain the compound with an oil-like interior which absorbs the drug and acts as a carrier. Paclitaxel’s solubility was increased 5,000 times as a result of this technology, and opened the door for further applications. One of these applications became Angiotech’s first, and best-known product, the TAXUS coronary stent. This paclitaxel-eluting system for the treatment of coronary heart disease is a vast improvement over bare metal stents, and is on track to become an industry standard. When the balloon catheter is inflated, bare metal stents can cause tears in the artery wall that lead to restenosis, the growth of scar tissue that can trap the stent or re-block the artery with tissue. TAXUS, with its paclitaxel-eluting technology, paralyzes cells to prevent their attraction to the site of injury, regulating scar growth and dramatically reducing the occurrence of restenosis. In the first 18 months after its launch in the United States in 2004, the product was implanted in more than two million patients. Today, TAXUS stents are implanted in four million patients worldwide and Angiotech is a global-leader in drug-device combination products. Their successes earned the partners an

NSERC president Suzanne Fortier NSERC Synergy Award for Innovation in 2006, a prize that recognizes outstanding examples of university-industry partnerships. Today, Dr. Burt receives NSERC funding through the Discovery Grants program and continues her lab’s fruitful relationship with the pharmaceutical company as the Angiotech Professor of Drug Delivery. This collaboration has demonstrated value that goes beyond the benefits of breakthrough research. It has provided training for many undergraduate, graduate students and postdoctoral fellows, given Angiotech a pipeline of talent already familiar with the company’s research and direction, and has enhanced the funding for the Faculties of Pharmaceutical Sciences and Medicine at UBC. Angiotech supports co-op and summer students, and company representatives participate as speakers and presenters at university functions. “The collaborative research between my UBC lab and Angiotech has resulted in a tremendous growth in research productivity and graduate training within my research group,” says Burt. “Many of my former grad students are now working at Angiotech and our joint publications demonstrate our close ties.” For more information on NSERC’s Strategy for Partnerships and Innovation, visit their website at www.nsercpartnerships.ca.

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NEW PRODUCTS Detection Kits PBL InterferonSource introduces Quansys Q-PlexTM Cytokine Multiplex ELISA arrays and high-throughput interferon detection kits for drug discovery and clinical research efforts in the treatment of infectious diseases and autoimmunity. Q-PlexTM kits combine various cytokine antibodies within multiplex arrays to give researchers a better understanding of the simultaneous relationship between multiple cytokines. The fully quantitative ELISA-based tests contain up to 16 distinct capture antibodies in each well of a 96-well plate. Each spot is well defined and represents a distinct antibody population. Up to 84 different samples can be assayed for all 16 unique cytokines in less than 2.5 hours.

Reply Card #4676 GFM Pro Flowmeter The Thermo Scientific GFM Pro Flowmeter is designed for continuous real-time measurement of gas flows, ensuring accurate and reproducible chromatography. With the capability to measure both positive and negative vacuum flows from 0.5 to 500 mL/min and -0.5 to -500 mL/min, the CE-certified probe can measure the volumetric flow of any gas with an accuracy of +/- 2 percent, ensuring excellent column to column reproducibility. The unit also protects itself against excessively high flow rates by deploying an automatic shut-off when the measured flow exceeds 600 mL/min. With an explosion-proof rating, this probe is ideal for use with any gas, even those that are flammable or explosive. Specifically designed for use with gas chromatography (GC) systems, the probe is applied directly to the gas flow stream, and the actual measured flow rate is displayed clearly on the LCD screen. The probe can be used as a bench-top or hand-held unit, and its ergonomic design and side grips provide extended durability. Furthermore, data can be easily saved and stored on a USB device for accurate monitoring of flow values over longer time periods. The unit is compat26 BIOTECHNOLOGY FOCUS FEBRUARY 2010

ible with all laboratory gases without the need for any prior knowledge of the gas composition.

Reply Card #4677 Software Syrris Atlas Reporting Software enables easy graphical analysis of sophisticated log files generated by the Atlas Base Unit, Atlas Software or Atlas Syringe Pump. Graphs can be created in seconds using the software, which incorporates an easy-to-use, “drag and drop” interface. Compatible with a range of Atlas products, the Reporting Software facilitates the fast analysis of resulting data for increased laboratory efficiency. Log files from Atlas modules and other software are uploaded using a USB stick to the Reporting Software enabling graphs to be created, customized and printed, quickly and easily. Multiple files can be imported simultaneously, allowing various parameters from different experiments, such as temperature, pH, stirrer speed, flow rate and turbidity to be plotted on the same graph for comprehensive batch-to-batch analysis. Comments added by the user during the experiment can also be displayed, while a line on the graph indicates when the comment was added, demonstrating correlations between any observations and the data.

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Titrator JM Science’s AQUACOUNTER® Coulometric Karl Fischer Titrator (AQ-300) has state-of-the-art performance features like a fritless cell option and it offers fast and accurate results. This reliable, easy-to-use coulometric titrator 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. This unit has balance and computer interfaces for GLP and ISO documentation. Choice of ion exchange or fritless cell system and thermal printer or impact printer are available. Printout contents include date, sample number, measurement value (µgH20), sample quantity, moisture content, mean value, standard deviation, CV, moisture quantity-time curve, and other preset titration parameters. Laboratories with limited budgets will benefit from this low-cost, highly productive unit. The unit is CE approved, has an international voltage input (100-240V) and results may be printed on an optional printer or downloaded to a PC. Includes download software for transferring results to a laptop or PC.

Reply Card #4679 Sample Preparation Norgen Biotek announces the expansion of its basket of urine-based sample preparation products. The kits can be used to preserve, concentrate and purify macromolecules such as DNA, RNA, microRNA, proteins, exfoliated cells and microorganisms from less than one millilitre up to 50 millilitres of urine. The sensitivity and speed make these kits very useful and powerful tools for isolating high quality analytes from urine for applications not only in biomarker discovery and diagnosis but also in the monitoring of renal and other diseases. Moreover the preservative kit is convenient and very useful for preserving macromolecules during shipping at ambient temperature. Reply Card #4680


NEW PRODUCTS Spectrophotometer The Thermo Scientific Evolution 60S UV-Vis spectrophotometer is a powerful high-resolution instrument designed with the flexibility to perform QA/QC, life science and general research methods. The Evolution™ 60S, with its 1.0 nm spectral bandwidth, is designed to meet the stringent requirements of international pharmacopeias and offers validation tools and protocols for customers in the regulated marketplace. Reply Card #4681

tive amount of ultraviolet light in the LCD display. The wide Luminosity range covers 0 to 130k lx and Low Light Resolution to 0.01 lx. The UV Range covers 0 to 30 mw/cm2. Internal Accumulation of Exposure is for both Light and UV. The TR-74Ui has a wide range from 10 to 99% Relative Humidity along with an expanded Temperature range from 0° to +55°C. This compact, lightweight unit is approximately 2” X 3” and operates on one AA battery and can store up to 8,000 readings times 4 channels for a total of 32,000 readings in One-Time or Endless

recording mode. Simply by connecting to a computer via a USB port, the recorded data can be quickly downloaded with the easyto-use software.

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Spectrophotometer Thermo Fisher Scientific Inc. unveils a new easy-to-navigate version of its interactive UV-Visible (UV-Vis) spectrophotometer web tool. The online platform has been upgraded to include the latest additions to the Thermo Scientific UV-Vis spectrophotometer product line. The tool serves as a webbased selector guide for the company’s UV-Vis spectrophotometers, software and accessories. Users are guided through the instrument selection process with a series of simple questions that identify the best instrument and accessory combination to meet their requirements. A section dedicated to general laboratory applications helps users configure their spectrophotometer, whether they are replacing an existing instrument or purchasing for the first time. Customers with more specific application requirements can easily contact a Thermo Fisher Scientific representative by completing an online contact form.

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UV Recorder The TandD TR-74Ui Illuminance UV Recorder can simultaneously measure and record four parameters: illuminance, ultraviolet light (UV), temperature and humidity. In addition to these parameters, the TR-74Ui is also capable of displaying cumulative illuminance and cumula-

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For a quick response please fax: 905-727-4428 or e-mail: circulation@promotive.net FEBRUARY 2010 BIOTECHNOLOGY FOCUS 27


CALENDAR FEBRUARY 2010 February 8-9 Bio CEO & Investor Conference Venue: New York City, NY Tel: (866) 356-5155 or +1.202.962.6666 Email: biopartnering@bio.org Web: http://ceo.bio.org/opencms/ ceo/2010/

February 22-23

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Company & Advertiser Index

March 16-17 6th Annual Pharma/Biotech Accounting and Reporting Congress Venue: Philadelphia, PA Email: tekoch@deloitte.com Web: www.nxtbook.com/ nxtbooks/advanstar/cbi_ accountingreporting2010/#/0

COMPANY

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Aeterna Zentaris Inc................................. 9.................................. Allon Therapeutics Inc............................. 8.................................. BC Centre for Disease Control................. 7.................................. BioMS Medical Corp................................. 9.................................. Bioniche Life Sciences Inc........................ 9..................................

Managing Legal & Business Risks in Clinical Trials in Canada Venue: Toronto, ON Tel: (416) 927-0718 Ext. 308, Email: j.chung@CanadianInstitute.com Web: www.canadianinstitute.com/ clinicaltrials.htm

March 31 North Ontario BioEnergy Trade Show Venue: Thunder Bay, ON Phone: (705) 472-2280 E-mail: info@canbio.ca Web: www.canbio.ca

BioSyntech Inc........................................ 10.................................

February 23

APRIL 2010

Canadian Light Source............................. 6..................................

TBI President’s Awards Gala “A Celebration of Success” Tel: 416-426-7293 Email: admin@ontbi.org Web: www.ontbi.org

April 6-7

February 23-25 Cold Chain Management & Temperature Control Summit Venue: Toronto, ON Tel: 1-800-882-8684 Email: info@iqpc.com Web: www.coldchainpharm.com

February 28-March 5 Pittcon 2010- Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy Venue: Orlando, FL Tel: (412) 825-3220 Email: info@pittcon.org Web: www.pittcon.org

MARCH 2010 March 8-10 Bio-Europe Spring 2010 Venue: Barcelona, Spain Email: tvoigt@ebdgroup.com Web: http://www.ebdgroup.com/bes/

March 8-12 4th Annual Growing the Margins: Green Energy and Economy for the Farm and Food Sectors Venue: London, ON Tel: (416) 426-7029 Fax: (416) 426-7280

28 BIOTECHNOLOGY FOCUS FEBRUARY 2010

BioFinance 2010 Venue: Toronto, ON Email: sadolfo@biofinance.ca Web: www.biofinance.ca

Biotalent Canada......................................... 5.............................4667 Brady.............................................................. 9.............................4669 Caledon Laboratory Chemical.................. 7.............................4668

Caprion Proteomics Inc.......................... 10................................. Cardiome Pharma Corp........................... 9.................................. Children’s Miracle Network...................... 23............................ 4674 Equicom Group........................................ 9..................................

April 14

Eppendorf.................................................... 32............................4685

12th Annual LifeSciences British Columbia Awards Venue: Vancouver, BC Phone: 604-602-5261 Email: pyeung@lifesciencesbc.ca Web: www.lifesciencesbc.ca

Fisher Scientific............................................ 2.............................4666 GEA Westfalia Separator Canada Inc........ 13.........................4671 IntelGenx Technology Corp..................... 9.................................. Island Labs............................................... 8.................................. Labopharm Inc......................................... 9..................................

MAY 2010

Merck & Co............................................... 9..................................

May 3-6

Microbix Biosystems Inc......................... 10.................................

BIO International Convention Venue: Chicago, IL Web: www.convention.bio.org

Miraculins Inc.......................................... 10.................................

JUNE 2010 June 1-2 EuroMedtech 2010 Venue: Leipzig, Germany Web: www.ebdgroup.com/emt/

Nuvo Research Inc................................... 9.................................. POI..................................................................31............................4684 Protox Therapeutics................................ 6.................................. Sanyo.............................................................11............................4670 Stellar Pharmaceuticals Inc...................... 8.................................. The Biotechnology Initiative.....................19............................4672

June 2-5

Therapure Biopharma Inc.................... 8, 10, 21.......................4673

13th Annual Canadian Society for Pharmaceutical Sciences Symposium Venue: Richmond, BC Web: www.cspscanada.org

Theratechnologies Inc........................... 6, 9................................

June 8-10

VWR............................................................... 25............................4675

Bio Energy Conference Venue: Prince George, BC Web:www.bioenergyconference.org

WEX Pharmaceuticals Inc......................... 9..................................

Transition Therapeutics Inc..................... 9.................................. University of Western Ontario.................. 6..................................

YM BioSciences Inc................................... 9..................................



THE LAST WORD

Energy Innovation and Commercialization

on the Prairies

By Carol Reynolds and international organizations to advance this biofuels project to the commercialization stage. Advancements in crop genomics also have the potential to unlock keys for plant breeders to focus on the production of crops with traits more suitable for the biofuel and food industries, while enhancing food traits. For example, producing a flax variety higher in omega-3 fatty acid content increases the plant’s functional food value. Using genomics research and plant breeding techniques to grow flax with additional foliage could also increase its biofuel producing potential. Having both traits in the same plant has the potential to increase productivity immensely.

Finding bugs to help the oil industry

E Carol Reynolds Director, Communications and Government Relations

nergy, innovation and commercialization - the buzzwords are everywhere these days in government, industry and academic circles. What’s all the buzz about? In the world of genomics research, it’s all about finding out how things work – or what makes up living organisms – and how can we use this knowledge to provide leaner, greener, more efficient ways to help our world’s energy supply. Genome Prairie is a not-for profit organization working with the Manitoba and Saskatchewan bioscience communities to discover the potential for alternative methods and sources of energy production and recovery. From enhanced oil recovery and agricultural waste biofuel production, genomics research holds the key to creating ways to conserve energy and provide sustainable options for our country’s future.

Converting biodegradable waste materials into biofuels A new project, based out of the University of Manitoba, aims to help farmers to be more productive, while helping to improve our energy supply. Microbiologists in Winnipeg are working to identify which types of bacteria can be used to transform waste products into ethanol, hydrogen and bioplastics. Methods are being studied to break down agricultural waste products, such as straw, flax shives and woodchips, into biofuels. Using genomics science, researchers are collecting and identifying bacteria which will carry out the breakdown of waste in the most efficient, cleanest manner possible. The potential impact on the energy industry is to provide an alternative source for biofuel production. Agricultural waste is used instead of simply being disposed of, adding another layer of utility to existing crops, making them more productive and lessening the “food vs. fuel” debate. Investment in this project by the Province of Manitoba shows its commitment to research and is paving its path to becoming a leader in the production of biofuels and bioplastics. Genome Prairie is working closely with the Province, the University of Manitoba and other national 30 BIOTECHNOLOGY FOCUS FEBRUARY 2010

The oil industry is challenged with getting the most out of the wells it drills - literally. It is not uncommon to have up to 50 per cent residual oil left in drilled wells, simply do to a lack of effective recovery methods. Phase One of a new genomics research project involving Genome Prairie, Enterprise Saskatchewan, Dycor Technologies Ltd. (Alberta) and Midwest Research Institute (Missouri), is hoping assist with oil recovery and to help get more out of the ground. The Microbial Enhanced Oil Recovery (MEOR) project’s goals include the identification of microorganisms which will react and break down barriers, resulting in more efficient oil flow from wells. This new biotechnology has the potential to reduce costs for industry and to offer an alternative to using chemicals and other labor-intensive methods to retrieve the oil. The success of this project will also lead to more efficient and lower water usage in traditional oil extraction methods, thus positively impacting conservation efforts. Saskatchewan continues to build its knowledge economy through the support of innovative projects such as MEOR. The Province’s project support underscores its efforts to maintain a reputation as a leading innovation, research and development destination. The potential technology commercialization opportunities resulting from this project are promising. The project has already attracted interest from the industry players who have dormant wells. The opportunity may exist for these wells to be reactivated and to have residual oil recovered. These two projects are led by Genome Prairie, a not for profit organization managing large scale genomics projects in Saskatchewan and Manitoba. Genome Prairie collaborates with researchers in both provinces on projects related to agriculture, health, energy as well as the societal impacts of genomics. Projects are supported by the Government of Canada through Genome Canada, and Western Economic Diversification, the Provinces of Manitoba and Saskatchewan and numerous academic institutions and industrial partners. www.genomeprairie.ca

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