Biotechnology Focus February/March 2015

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

FEBRUARY/MARCH 2015 VOLUME 18, NUMBER 1

IT’S NOT EASY

BEING RARE

THE CHALLENGES SURROUNDING PUBLIC REIMBURSEMENT FOR RARE DISEASE DRUGS

INSIDE: SPECIALTY DRUG PRICING: WORTH RISKING PAYOR WRATH

Publication Mail Registration Number: 40052410

TAKE YOUR PICK FROM HUNDREDS OF THOUSANDS OF PRODUCTS The products you need to further scientific research

VWR has All You Need for Proteomics and Food Analysis.

Offering the most extensive product portfolio and services to meet your research needs.

Contact your VWR Sales Representative for more information!

1.800.932.5000 / ca.vwr.com

contents FEBRUARY/MARCH 2015 – VOLUME 18 – NUMBER 1

13

13 Specialty Drug Pricing: Worth Risking Payor Wrath

FEATURES SPECIALTY DRUG PRICING: WORTh RISKING PAYOR WRATh There’s been a lot of discussion around pricing for specialty drugs, payor pushback and how it impacts investors. Roberto Bellini highlights some of the important themes to watch.

(By Roberto Bellini)

16 It’s not easy being rare Opinion

15 17

IT’S NOT EASY BEING RARE The challenges surrounding public reimbursement for companies developing rare disease drugs.

(By Joanne Koskie and Christine Beyaert)

PERSONALIZED MEDICINE: PATENTING CONTROVERSIES Whether diagnostic and personalized medicine technologies can be patented has been hotly debated in a number of jurisdictions. Court challenges recently launched in Canada bring the controversy to our backyard.

(By Carmela DeLuca and Katherine Bonter)

20

Towards providing appropriate, timely, and sustainable access to therapies for rare disease patients and other targeted patient subgroups living with more common conditions.

(By Durhane Wong-Rieger)

DEPARTMENTS 6 9 28 30

RESEARCh NEWS BUSINESS CORNER NEW PRODUCTS CALENDAR OF EVENTS

IN EVERy ISSUE

6 RESEARCh NEWS

New antibody therapeutics company, Northern Biologics, launched

ion! om www.biotechnologyfocus.ca

AN OPEN LETTER TO CANADA’S hEALTh MINISTERS REGARDING RARE DISEASE DRUGS

24

ACROSS CANADA Searching for PROOF of Person-Specific Prevention and Care (By Bruce McManus)

February/March 2015 BIOTECHNOLOGY FOCUS 3

PUBLIShER’S NOTE

PUBLISHER/ EDITOR-IN-CHIEF SENIOR WRITER CONTRIBUTING WRITERS

Terri Pavelic Shawn Lawrence Bruce McManus Carmela DeLuca Christine Beyaert Durhane Wong-Rieger Joanne Koskie

Inching closer to a ‘Canadian Orphan Drug Policy’

Katherine Bonter Noel Courage

CONTROLLER MARKETING MANAGER CIRCULATION DIRECTOR

Laskey Hart Elena Pankova John R. Jones Mary Malofy Mary Labao circulation@promotive.net Tel: 289-879-4272

EDITORIAL ADVISORY BOARD Christine Beyaert, Cohn&Wolfe; Rob henderson, BioTalent Canada; Najla Guthrie, KGK Synergize; Pierre Bourassa, IRAP, Montréal; Murray McLaughlin, Sustainable Chemistry Alliance; Carol Reynolds, AdFarm; Ulli Krull, UTM; John Kelly, KeliRo Company Inc.; Peter Pekos, Dalton Pharma Services; Brad Thompson, Oncolytics; Darrell Ethell, CanReg; John hylton, John H. Hylton & Associates; Robert Foldes, Viteava Pharmaceuticals Inc.; Randal R.Goodfellow, P.Ag., Senior Vice President, Corporate Relations, Ensyn; Bob h. Sotiriadis, Robic LLP; Dale Patterson, Genome Canada; Darcy Pawlik, Syngenta Seeds Canada Inc; Gail Garland, OBIO; Barry Gee, CDRD; Bonnie Kuehl, Scientific Insights Consulting Group Inc.; Raphael hofstein, MaRS Innovation Biotechnology Focus is published 6 times per year by Promotive Communications Inc. 23-4 Vata Court, Aurora, Ontario L4G 4B6 Phone 905-727-3875 Fax 905-727-4428 www.biotechnologyfocus.ca E-mail: biotechnology_focus@promotive.net Subscription rate in Canada $35/year; USA $60/year; other countries $100/year. All rights reserved. No part of this publication may be reproduced without written consent. Publications Mail Registration Number: 40052410 Return undeliverable Canadian addresses to: circulation dept – 23-4 Vata Court, Aurora, Ontario L4G 4B6 National Library of Canada ISSN 1486-3138 \

twitter.com/biotechfocus linkedin.com/company/biotechnology-focus google.com/+biotechnologyfocuscanada

IN

Roberto Bellini ACCOUNT MANAGER GRAPHIC DESIGNER

It seems more and more that our newsfeed is trumpeting announcements around new submissions, designations and approvals for orphan drugs. In Canada, where an estimated 2.8 million people live with one of the more than 7,000 identified rare diseases, the imminent and long awaited implementation of an Orphan Drug Regulatory Framework is equally newsworthy. Clearly orphan drugs are trending up and there’s no indication of a slowdown any time soon.

In this issue, we’ve striven to keep the orphan drug conversation going.

To kick things off Canadian Organization for Rare Disorders president Durhane WongRieger proposes a pan Canadian “solution” to improving access to orphan drugs. Her open letter to government emphasizes a “sensible, sustainable” program or managed access schemes (MAS) as a standard strategy for supporting innovative targeted therapies.

Next, Joanne Koskie and Christine Beyaert discuss the challenges surrounding public reimbursement for companies developing rare disease drugs. Some of their key points include adapting unique health technology assessment (HTA) policies for orphan drugs different than the HTA for traditional drugs. They also suggest taking a multi-stakeholder, multi-channel approach that strategically integrates advocacy with government and media relations in order to stress the importance of approving drugs for rare diseases.

Rounding out the orphan drug trifecta, Roberto Bellini says recently there’s been a lot of discussion around pricing for specialty drugs, payor pushback and whether it is impacting investor interest in specialty drug companies. His findings are quite surprising.

Other key stories in this issue include two separate pieces on patent protection and personalized medicine from the folks at Bereskin & Parr, as well as a Pan Canadian piece on biomarkers from leading researcher and scientist Bruce McManus.

Overall, we think this issue is a great way to kick off 2015! We hope you enjoy it too!

c

All opinions expressed herein are those of the contributors and do not necessarily reflect the views of the publisher or any person or organization associated with the magazine.

If you would like to order hard copy or electronic reprints of articles, contact Sandra Service 905-727-3875 x228 reprints@promotive.net

R

Em us en pr an

facebook.com/biotechnologyfocus 4 BIOTECHNOLOGY FOCUS February/March 2015

us

cellIQ

TM

INTELLIGENT CO2 INCUBATOR

Smart TOUCH SCREEN INTERFACE

2min CO2 RECOVERY

8x Faster DECONTAMINATION

Rethink cell growth.

Empower your cell culture through the most advanced user interface and technology. Optimize your stem cell’s environment with a new intelligent touch screen for precise CO2 recovery, uniform temperature control, and rapid decontamination.

us.panasonic-healthcare.com/celliqseries

Distributed in Canada by ESBE Scientific | info@esbe.com

R & D NEWS Merck joins Structural Genomics Consortium (SGC) Toronto with $7.5 million contribution

(From left to right) Dr. Ronan O’Hagan, Dr. Aled Edwards, The Honourable Reza Moridi, Mr. Chirfi Guindo and Ms. Jennifer Chan. (CNW Group/Merck) The Structural Genomics Consortium (SCC) Toronto announces it has added global pharma giant Merck as its newest member .

In addition to joining the consortium as a partner, Merck is contributing $7.5 million to the network. The money will go towards supporting projects with a focus on precompetitive research. One of the projects includes developing small inhibitory molecules called chemical probes to study epigenetic mechanisms of regulation. In collaboration with leading clinical institutions in Ontario and around the world, use of the probes will expand the understanding of biology in multiple disease areas, particularly cancer and inflammatory diseases.

According to Merck Canada Inc. president and managing director Chirfi Guindo, the SGC’s track record for delivering high-quality science, along with Toronto’s ecosystem of world-class hospitals and research labs as well as a strong commitment of collaboration between government and industry, make the SGC an ideal research partner.

“At Merck, we strive to identify and support research areas that will have the most impact on fulfilling the unmet medical needs of patients, who are at the core of everything we do,” he said. “In Canada, Merck is very pleased to be able to encourage innovation and research across an established SGC collaborative network 6 BIOTECHNOLOGY FOCUS February/March 2015

of more than 250 academic laboratories at leading institutions.”

Developing an “open source” publicprivate partnership The SGC is creating an “open source” publicprivate partnership that generates knowledge, technologies, and research tools to discover and characterize “pioneer” drug discovery targets. The partnership will leverage past and future investments made into the SGC by its public and private sector funders, and SGC’s large network of collaborators based at leading academic institutions worldwide. The overarching aim of the partnership is to enable private sector funders to advance a significant number of pioneer targets into proprietary drug discovery programs.

“At the heart of our partnership is a commitment to transparency and quality,” said Dr. Aled Edwards, founding and current CEO of the Structural Genomics Consortium (SGC).

The SGC is funded by Abbvie, Bayer, Boehringer Ingelheim, the Canada Foundation for Innovation, Eli Lilly Canada, Genome Canada, GlaxoSmithKline, Janssen, Merck Canada, Novartis, the Ontario Ministry of Research & Innovation, Pfizer, Takeda, and the Wellcome Trust.

To see this story online visit http://biotechnologyfocus.ca//?p=13640

Clinical Trials & Patents ProNAi Therapeutics Inc. (Vancouver, BC) reports that the first patient with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) has enrolled in the company’s “Wolverine” Phase 2 study and been treated with PNT2258. The patient was treated by Dr. Wael Harb, founder of the Horizon Oncology Center in Lafayette, IN. The multi-center, singleagent, open-label, Phase 2 investigation of PNT2258 will characterize anti-tumour activity and collect safety data on approximately 60 patients with relapsed or refractory DLBCL. The primary endpoint is overall response rate, assessed by FDG-Positron Emission Tomography (PET) scan and compared to relevant historical controls. Secondary outcome measures include disease control rate, progression-free survival, overall survival and exploratory predictors of outcome assessed by tumour biopsy and pharmacodynamics sample analysis.

n

ProMetic Life Sciences Inc. (Laval, QC) orally active anti-fibrotic lead drug candidate, PBI-4050, has been approved to commence a clinical trial in patients suffering from idiopathic pulmonary fibrosis (IPF) following the CTA clearance by Health Canada. The objectives of the 12 weeks open-label, single-arm, exploratory Phase 2 study are to evaluate the safety and tolerability of PBI-4050 in 40 patients suffering from IPF and to gather data on the effects of PBI-4050 on pulmonary function, disease progression and inflammatory/ fibrotic markers. ProMetic successfully completed its PBI-4050 Phase 1 clinical trial in 40 healthy volunteers, in which it was found to be safe and well tolerated with no serious adverse events. The company has also started enrolling patients with diabetic kidney disease (DKD) in the multi-dose part of the Phase 1b trial and is expected to report results by the end of the first quarter of 2015.

n

n Qu Biologics (Vancouver, BC) has enrolled

the first two participants in its Phase 2a clinical trial for lung cancer. The trial is an open label, single-arm, exploratory study to evaluate the safety, tolerability, compliance and mechanism of action of QBKPN site specific immunomodulation (SSI) in subjects with two or more second primary pre-invasive or invasive adenocarcinoma following surgical resection of stage 1 non-small cell lung cancer. The trial is taking place at the BC Cancer Agency Research Centre under principal investigator Dr. Stephen Lam. QBKPN SSI is derived from components of inactivated K. pneumoniae bacteria, and is designed to activate an anticancer immune response in the lungs.

For more R&D news visit http://biotechnologyfocus.ca/ category/topics/science/

R & D NEWS Innovation Squared: MaRS Innovation and Johnson & Johnson Innovation partner MaRS Innovation, the commercialization agent for 15 of Ontario’s leading academic institutions, has struck a research collaboration deal with Johnson & Johnson Innovation, LLC and its Canadian affiliate, Janssen Inc. The two sides say they will collaborate on projects to advance three technologies focused on cardiac, diabetes and depression, respectively.

“These three projects reflect the quality of innovation present in Toronto’s research community for our industry partners, and Toronto’s progress in addressing healthcare issues of international concern,” said Dr. Raphael Hofstein, president and CEO of MaRS Innovation. “Johnson & Johnson Innovation is a long-term strategic partner of MaRS Innovation and of our members; our collaboration reflects the benefits to accessing our members’ deal flow through MaRS Innovation. Through these deals and other scientific exchanges, we see increased interest in Toronto’s innovation and entrepreneurship community.”

The projects’ principal investigators are researchers from the University Health Network (UHN), the Centre for Addiction and Mental Health (CAMH) and the University of Toronto. The projects to be supported by the deal include: • IMPROVING CARDIAC SURGERY OUTCOMES — Through work at UHN’s Peter Munk Cardiac Centre, researchers are developing new technology to detect electrical drivers in patients with atrial

fibrillation, a common type of arrhythmia. Preliminary testing suggests this technology may increase the success of atrial fibrillation catheter ablation, which depends upon accurately locating focal electrical sources when scanning the heart.

• BLOOD TEST FOR DEPRESSION — Investigators at CAMH and Indoc Research are testing a new peripheral blood biomarker for major depressive disorder that may help to identify when a patient is experiencing or at risk of developing the disorder. The biomarker may also help researchers to develop new therapeutics for treating the condition.

• DIAGNOSTIC FOR GESTATIONAL AND TYPE 2 DIABETES — University of Toronto research has identified a specific metabolite elevated in both gestational and type 2 diabetes patients. Researchers are examining if this metabolite could serve as a predictive diagnostic for the diseases.

This announcement follows Johnson & Johnson Innovation’s December 2013 commitment to collaborate on early-stage drug development projects.

To see this story online visit http://biotechnologyfocus.ca//?p=13566

Life Sciences Ontario Annual Awards Gala Dinner Recognizing 2015 Award Recipients Reserve your table or ticket today

February 25, 2015 at Liberty Grand, Exhibition Place, Toronto Lifetime Achievement Award: John Oliver, B.S.A., Chairman, Flax Canada 2015 Inc.; Advisory Board, Canadian Agri-Food Policy Institute and President, Maple Leaf Bio-Concepts & Lojon Associates International LSO Volunteer Award: Christine Beyaert, Counsellor, Cohn & Wolfe

Public Service Award: Dr. Deb Stark, MBA, Deputy Minister of the Ministry of Agriculture, Food and Rural Affairs

Community Service Award: Dr. Luis Barreto MBBS, MD, MHSc, President, Dr. Luis Barreto & Associates & Special Advisor, Vaccine Program, Human Health Therapeutics, Canada’s National Research Council (NRC).

Life Sciences Company of the Year: Xagenic Inc. Shana Kelley, Founder & Chief Technology Officer

For more information on registration and sponsorship phone: 416-426-7293 or email: admin@lifesciencesontario.ca.

More details will be posted on www.lifesciencesontario.ca February/March 2015 BIOTECHNOLOGY FOCUS 7

R & D NEWS

Montréal-based biotechnology company enGene Inc. reports it has closed a $13.5 million Series B investment round.

The financing round was led by Forbion Capital Partners, with Québec’s Fonds de solidarité FTQ and Pharmstandard International S.A. participating as new investors in the company. Existing investor Lumira Capital via its Merck Lumira Biosciences Fund, which led the Series A round in 2013, also participated.

The company is developing a platform technology for delivering genes including DNA or RNA to cells lining the gastrointestinal tract, effectively turning the gut into a protein factory. enGene is initially applying its unique platform technology to deliver immune-modulating biologics to the intestine and has demonstrated efficacy as a mucosal immunotherapy in several animal models for autoimmune diseases including, inflammatory bowel disease (IBD) and Type 1 diabetes.

Proceeds from the series B financing

round will be used to advance enGene’s lead product, EG-12, into Phase 1/2 clinical trials. EG-12 consists of a unique carrier-DNA complex that provides gut-localized expression of IL-10 being developed for the treatment of ulcerative colitis (UC). IL-10 is an anti-inflammatory cytokine and individuals with genetic defects within the IL-10 signaling pathway suffer from severe early-onset inflammation of the gut.

“We have demonstrated that this proprietary platform technology can be used effectively to localize delivery of protein drugs to the gut,” said Dr. Anthony Cheung, president and CEO of enGene. “Another recent exciting development is that we have succeeded in turning our drug formulation into an orally available ‘gene pill’. This breakthrough has unlocked the huge potential of enGene’s core technology in enabling delivery of protein-based drugs via the oral route.”

Dr. Cheung adds that part of the proceeds from the financing will be used to develop

Dr. Anthony Cheung

enGene raises $13.5 million to develop intestinal gene delivery platform

a ‘gene pill’ to achieve oral delivery of a long-acting insulin and GLP-1 analog for subjects with Type 2 diabetes.

To see this story online visit http://biotechnologyfocus.ca//?p=13575

NRC, Lilly Creek and AMRIC join forces on vaccine to prevent gastritis, ulcers and gastric cancer

(L to R) Sean Thompson, President and CEO of Lilly Creek Vaccines, Francisco Diaz-Mitoma, CEO & Scientific Director of AMRIC and Jim Richards and Eleonora Altman from NRC visit Lilly Creek Vaccines in Sudbury to announce an agreement to develop a new vaccine to combat Helicobacter pylori infection in Canada (Photo credit: NRC) Vaccines have the power to prevent infections that cause cancer – familiar examples include Gardasil and Cervarix to prevent HPV infections that cause cervical cancer. Researchers at the National Research Council of Canada (NRC), the Advanced Medical Research Institute of

8 BIOTECHNOLOGY FOCUS February/March 2015

Canada (AMRIC) and Lilly Creek Vaccines are harnessing this principle to develop a new vaccine to combat and eradicate Helicobacter pylori (H. pylori) infection in Canada.

As part of this two-year, $575,000 agreement, NRC’s Vaccine Program will design a candidate vaccine using glycoconjugate

antigens that stimulate the immune system. NRC will also carry out preclinical testing to determine its efficacy. H. pylori infection affects about 50 per cent of the world’s population – 70 per cent in developing countries and 20 to 30 per cent in industrialized countries, with most infections occurring in childhood. The infection causes gastritis in almost all cases, peptic ulcers in 10 to 15 per cent of cases, and gastric cancer in about 1 per cent of cases. A class 1 carcinogen, H. pylori increases the risk of gastric cancer six-fold. Particularly at risk for H. pylori infections are Canada’s northern communities, where infection rates range from 50 to 60 per cent compared to about 20-30 per cent nationally.

If results from the new program are positive, preclinical research and clinical trials in high-risk populations in northern Canada will be conducted by Lilly Creek Vaccines, a new venture created by AMRIC a Health Sciences North hospital affiliated research institute that aims to improve health care outcomes in Northern communities and across Canada.

To see this story online visit http://biotechnologyfocus.ca//?p=13588

BUSINESS CORNER FedDev provides a boost to Dalton Pharma Services

From L to R: Minister for the Federal Economic Development Agency for Southern Ontario Gary Good year, Member of Parliament for York Centre Mark Adler and Dalton Chemical Laboratories President & CEO Peter Pekos Toronto-based pharmaceutical company Dalton Pharma Services reports it is expanding its manufacturing capacity with financial help from Ottawa.

The contract manufacturing and drug development research company is receiving more than $2 million from the Federal Economic Development Agency for South-

ern Ontario (FedDev Ontario) investing in business growth and productivity initiative. The company itself is putting in an additional $6.3 million to increase its manufacturing capacity.

Dalton will use the federal funding to buy equipment and renovate the company’s existing facility. Located in North York, Dalton Pharma Services has been in operation for 28 years. The company is a spin-off from York University and offers manufacturing, chemistry, and analytical services on a contract basis to the global biotechnology and pharmaceutical industries.

Additionally, the project is expected to create 21 new full-time position in the life science sector along with an additional 13 new positions following project completion. The company currently employs approximately 70 people.

“FedDev has provided an important contribution to our growth at just the right time for us to benefit,” said company president and CEO Peter Pekos, at a media event announcing the funding Friday, Jan. 16.

Since 2009, FedDev Ontario has invested $1.2 billion in businesses, leveraging another $1.5 billion in investment from the private sector.

To see this story online visit http://biotechnologyfocus.ca//?p=13563

Caprion to in-license Xpresys®Lung from INDI for Canadian commercialization Caprion has reached an exclusive agreement to in-license Xpresys Lung in Canada from Integrated Diagnostics® (INDI).

XpresysLung is a molecular diagnostic blood test that assists with the management of indeterminate lung nodules. The clinical laboratory developed test is currently only available in the U.S.. It could provide physicians with objective information to identify nodules with a high probability of being benign potentially reducing unnecessary invasive procedures, which may be risky for the patient and costly to the healthcare system. The blood test measures the relative abundance of proteins from multiple pathways associated with lung cancer, using a highly sensitive analytic technique called multiple reaction monitoring mass spectroscopy (MRM-mass spec).

“Xpresys Lung is an important addition to our clinical laboratory service business

and enables us to provide new diagnostic tools for physicians in Canada which may aid them in reducing unnecessary invasive procedures for benign lung nodules — generating economic efficiencies for our healthcare system,” said Martin LeBlanc, chief executive officer, Caprion.

The agreement marks the continuation of a long-standing collaboration between Indi and Caprion, which began with Caprion as an early partner of Indi in the proteomics clinical discovery of Xpresys Lung.

Indi launched the test in the US in 2013.

Caprion will hold the exclusive rights to market and commercialize Xpresys Lung in Canada, beginning with Quebec. Caprion will pay Indi royalties and several milestone payments. Exact financial terms of the agreement were not disclosed.

Caprion is receiving support for its Canadian Xpresys Lung commercial efforts from the Government of Québec as part of the

Personalized Medicine Partnership for Cancer (PMPC), a public-private partnership led by Caprion and focused on clinical biomarkers and personalized healthcare solutions to improve the outcome and cost-efficiency of healthcare services provided to cancer patients in the province of Québec.

To see this story online visit http://biotechnologyfocus.ca//?p=13603 February/March 2015 BIOTECHNOLOGY FOCUS 9

BUSINESS CORNER Amorfix announces move to San Francisco The Ontario life science sector will be down one company sometime in the first quarter of 2015 with the news that Amorfix Life Sciences Ltd. is closing its operations in Mississauga, ON and relocating to San Francisco, CA. “The San Francisco Bay Area is a dynamic hub for biotechnology and relocating the company is an integral part of our business strategy”, said Dr. Robert Gundel, Amorfix president and CEO. “We have already identified office and laboratory space, putting us in an ideal location to implement our business plan and grow the company.”

Dr. Gundel says that the move to California will be delayed to conserve cash until new investment funds are received. He adds that Amorfix will continue to focus on developing its neurodegenerative disease assets for ALS and Alzheimer’s disease.

For ALS, these assets include therapeutic antibodies that block misfolded SOD1 and a simple blood test diagnostic for early detection of the disease. For Alzheimer’s disease, the company has developed a ‘best

in class’ diagnostic that can accurately identify patients with early-stage disease.

The company is also in discussions with a number of firms concerning the development of its neurodegenerative assets, as well as strategic alliances and/or partnerships around the technologies. The company will continue to be a public company

listed on the TSX. Amorfix Life Sciences, Ltd was founded in 2004 by neuroscientist and physician Dr. Neil Cashman.

To see this story online visit http://biotechnologyfocus.ca/?p=13568

Dealmakers Cyclenium Pharma Inc. (Sherbrooke, QC) and the Institute for Research in Immunology and Cancer — Commercialization of Research (IRICoR) along with Université de Montréal and its Institute for Research in Immunology and Cancer (IRIC) (Montréal, QC) announce the signing of a collaborative research agreement. Cyclenium Pharma is a pharmaceutical company specializing in the discovery and development of novel drug candidates based on proprietary macrocyclic chemistry.

The collaboration intends to utilize Cyclenium’s proprietary QUEST Library™ of macrocyclic molecules and associated hit-to-lead optimization expertise in concert with IRIC’s capabilities in biological target identification, characterization and screening, as well as medicinal chemistry. The objective of the collaboration is to discover and develop new drug candidates for the treatment of cancer and immunological disorders.

n

n OncoGenex Pharmaceuticals, Inc. (Vancouver, BC) reports it has executed an initial agreement with Teva Pharmaceutical Industries Ltd. to regain the rights to custirsen, an investigational compound. The compound is currently being evaluated in a Phase 3 clinical trial as a treatment for prostate and lung cancers. The transfer of rights is connected with the termination of the collaboration agreement between OncoGenex and Teva executed

10 BIOTECHNOLOGY FOCUS February/March 2015

in 2009. The initial agreement reached by OncoGenex and Teva provides that following execution of the final agreement to terminate the collaboration between the parties, OncoGenex will receive a $27 million payment from Teva, subject to certain adjustments. In addition, OncoGenex will take over responsibility for all custirsen related expenses, including those related to the ENSPIRIT trial, as well as manufacturing and regulatory activities for custirsen programs, which are currently being managed

by Teva.

Cipher Pharmaceuticals Inc. (Mississauga, ON) reports it is expanding its dermatology product portfolio licensing the Canadian rights to Ozenoxacin, a topical treatment for adult and paediatric patients with impetigo, from Ferrer, a privately-held Spanish pharmaceutical company. In 2013, Ferrer successfully completed a first Phase 3 clinical trial of Ozenoxacin in adult and paediatric patients aged two years and older with impetigo.The study demonstrated the superiority of Ozenoxacin one per cent cream versus a placebo, applied topically twice daily for five days, on both the clinical and bacteriological endpoints by end of therapy visit. Ferrer commenced a second Phase 3 trial of Ozenoxacin in June 2014. The multicenter, randomized, double-blinded, clinical study comparing Ozenoxacin one per cent cream versus placebo will be conducted in approximately 412 patients

n

aged two months and older with a clinical diagnosis of non-bullous or bullous impetigo.

Ferrer anticipates that the second Phase 3 trial will be completed by the end of Q1 2015. Under the terms of the agreement, Ferrer will receive an upfront payment and is eligible for development milestones and revenues from product sales in Canada. Ferrer will manufacture Ozenoxacin and deliver finished product to Cipher.

Cipher Pharmaceuticals Inc. (Mississauga, ON) reports it has acquired the assets of Hershey, Pennsylvania-based life science company Melanovus Oncology Inc.. The assets include seven pre-clinical compounds for the treatment of melanoma and other cancers. Founded in 2012, Melanovus acquired an exclusive global license to a library of compounds and related intellectual property from the Penn State Research Foundation. The compounds originate from work done by Dr. Gavin Robertson, professor of pharmacology, pathology, dermatology and surgery at Penn State University, and director of the Penn State Hershey Melanoma Center. The transaction includes an upfront payment to Melanovus of US$500,000, as well as the payment of certain IP expenses related to patent prosecution and maintenance.

n

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

BUSINESS CORNER CTI Life Sciences raises new $134 million venture capital fund CTI Life Sciences reports the first closing of its second venture capital fund (CTI II), with $134 million of capital now available for investment.

The new fund includes reaffirmed support from CTI’s existing Québec institutional investors along with new investors Teralys Capital and BDC Capital via the Government of Canada’s Venture Capital Action Plan (VCAP).

Montréal-based CTI Life Sciences was established in 2006 with a $100 million first fund. The first fund has delivered a solid performance, with three successful exits to date including the US$ 1.1 billion acquisition of Enobia Pharma by Alexion Pharmaceuticals, one of the largest stage-adjusted deals thus far for a Canadian biotech company.

CTI Life Sciences says that CTI II will continue to invest predominantly in biotherapeutics and opportunistically in medical technologies and healthcare IT. The fund mainly seeks to build companies that develop assets at the pre-clinical to early clinical phase.

Its primary focus of investment will remain

in Québec and Canada where approximately two thirds of the investments will be located, with the remainder in the U.S. In line with its expanded reach, CTI has opened an office in the Northeast USA, which complements its main base in Montréal.

“This is an exciting time to invest in life sciences”, said Ken Pastor, general partner at CTI II. “We also have expanded our investment team and have benefited from fantastic support from our institutional investors,

without which this new fund would not have been possible. We now stand to grow and continue delivering superior financial performance.”

In addition to Jean-François Leprince, Ken Pastor and Shermaine Tilley, who were already managing partners in first fund, CTI II has recruited new US-based partner Janelle Anderson (ex-Merck) as well as new Montreal-based principal Laurence Rulleau.

“This new investment by the Fonds de solidarité FTQ shows our willingness to build on the success of the CTI I fund, as well as to continue building a performing Québec-based investment franchise for the health sciences sector,” declared Alain Denis, senior vice-president, New Economy, at the Fonds de solidarité FTQ. “With deep Québec roots, the CTI II fund will expand the availability of capital, one of three strategic assets Québec offers the sector, the other two being the availability of research and service infrastructures and an important pool of research talent.”

To see this story online visit http://biotechnologyfocus.ca//?p=13509

February/March 2015 BIOTECHNOLOGY FOCUS 11

BUSINESS CORNER Tekmira Pharmaceuticals to take over OnCore Biopharma in merger deal Tekmira Pharmaceuticals Corp. reports it has agreed to buy Pennsylvania-based OnCore Biopharma Inc. in an all stock merger deal.

Tekmira is currently best-known for its experimental therapeutic targeting the Ebola-Guinea virus. The company said it would continue its efforts in this area, as well as in oncology and other anti-viral programs following the merger.

The merger also combines both parties’ broad expertise in antiviral drug development, including Tekmira’s Phase 1-ready hepatitis B (HBV) RNAi therapeutic and OnCore’s multiple hepatitis (HBV) programs, to build a portfolio of compounds aimed at eradicating HBV. The new Tekmira’s most advanced products are expected to be TKM-HBV, an RNAi therapeutic designed to eliminate HBV surface antigen (HBsAg) expression, a key component of host immune suppression, which is on track to begin human clinical trials in the first quarter of 2015; and OCB-030, a second-gener-

ation cyclophilin inhibitor focused on the suppression of viral replication, as well as stimulation and reactivation of the body’s immune response, which is anticipated to enter human clinical trials in the second half of 2015.

Upon closing of the deal, OnCore will become a wholly-owned subsidiary of Tekmira with OnCore shareholders holding about 50

per cent of the total outstanding shares of Tekmira. Additionally, Tekmira’s chief executive Mark Murray will remain as CEO of the merged company and chairman Daniel Kisner will become vice chairman. OnCore’s chairman Vivek Ramaswamy will be the chairman of the combined company.

To see this story online visit http://biotechnologyfocus.ca/?p=13608

Zymeworks signs yet another deal with big biotech

Canadian biotech company Zymeworks Inc. has inked another deal with a biotech giant, this time teaming up with Celgene.

Under the terms of the agreement, Zymeworks and Celgene will collaborate on the research and development of multiple bispecific antibodies based on the Azymetric™ platform. The deal gives Celgene the right to develop and market an undisclosed number of antibody drug candidates that are designed to hit two biological targets instead of just one. Celgene will also have the option to advance the resulting bi-specific candidates through clinical development and subsequent commercialization.

One of the main attractions of Azymetric antibodies, which are manufactured us12 BIOTECHNOLOGY FOCUS February/March 2015

ing conventional monoclonal antibodies, is that they help to reduce drug development timelines significantly because they are easier to scale up on the manufacturing side.

“We are extremely excited to collaborate with Celgene on the development of bispecific antibodies using the Azymetric™ platform and believe that this class of biotherapeutics has the potential to create game-changing treatment options for patients with unmet medical needs,” said Dr. Ali Tehrani, president & CEO of Zymeworks.

Zymeworks will receive an initial upfront payment, as well as an equity investment of $10 million from Celgene. Zymeworks is eligible to receive clinical, regulatory, and

commercial milestones on successful candidates totaling up to US $164M per therapeutic candidate. Additionally, if any of the experimental drugs make it all the way to the market, Zymeworks will collect royalties on worldwide net sales. Further financial details are not disclosed.

“We believe that the upfront revenue from this collaboration, in combination with Celgene’s meaningful equity investment and the proceeds from our recent financing rounds, will help accelerate Zymeworks’ internal oncology pipeline candidates towards multiple INDs in 2016 and beyond,” said Dr. Tehrani.

Celgene is not the first company to take an interest in Zymeworks’ Azymetric™ platform. Other companies including Merck & Co., Inc. have also signed research and collaboration agreements with Zymeworks to access the platform for the development of novel bi-specific antibody therapeutic candidates. Likewise, Zymeworks also has a deal in place with Elli Lilly signed in October, 2014, focused on the development of an undisclosed number of novel bi-specific antibody therapeutics using the Azymetric™ platform for targets that could lead to new cancer immunotherapies.

To see this story online visit http://biotechnologyfocus.ca/?p=13600

By: Roberto Bellini

REIMBURSEMENT

specIalty Drug prIcIng:

was largely blown out of proportion - the losses in the NBI were recovered in a matter of days - Express Scripts’ deal was perceived by market watchers as a shot across the bow to drug companies that were used to more pricing leverage.

As the landscape shifts going forward, these are the important themes to watch.

Specialty Pharma Continues to Push Premium Pricing The poster child for pricing in specialty pharma is a drug called Acthar from Mallincroft.

It was first discovered over 50 years ago to treat infantile spasms and, until recently, sold for $50 per vial.

Over the last five years, Acthar has increased in price from $50 to $1,650, to the current price of $28,000 per vial, which translates into more than $100,000 per treatment course.

While that may seem high, it’s in line with many high priced specialty drugs, and particularly the ones that treat rare pediatric conditions like infantile spasms.

The vertiginous - and most often justified - pricing of rare disease drugs is the extreme example of specialty drug pricing. Combine the robust pricing with the fact that more and more traditional drugs are going generic, spending on specialty drugs is in line to surpass that of their traditional counterparts by 2018, according to data from market analytics firm Artemetrx (see Table 2).

Worth risking payor Wrath

O

n December 23rd of last year, the Nasdaq Biotech Index (NBI) dropped dramatically, plummeting nearly 300 points in one day and losing 8.5 per cent of its value. Despite the fall, the NBI, which tracks the performance of the most important Nasdaq-listed biotech companies, had an exceptional 2014 gaining over 35 per cent overall. In fact, the NBI has been one of the top performing indexes for the last five years, driven largely by increasing FDA approvals for new drugs, strong M&A activity and increased earnings.

So, what’s so important about one poor

trading day during one of the most significant bull runs in biotech history? The cause of the decline on December 23rd.

Before market open, Express Scripts, one of the largest pharmacy benefits managers in the United States, announced it would exclusively reimburse Abbvie’s newly approved Hepatitis C drug, Viekira Pak, in return for a significant discount to the list price. Most importantly, this deal froze out Gilead and its more expensive hepatitis C virus drug Sovaldi from the 25 million people in Express Scripts National Preferred Formulary.

While the threat of a pharma pricing war

Payors Are Fighting Back with More Exclusionary Deals Likely to Come Health plans and pharmacy benefit managers, like Express Scripts, have been very vocal about their opposition to high drug pricing. The Hepatitis C market in particular has been a lightning rod for this frustration following Gilead pricing their Sovaldi treatment at $84,000. Considering there are three to four million Hepatitis C patients in the U.S., the combination of pricing and patient numbers will result in a potentially massive bill for payors.

Table 1: Examples of Specialty Drug Pricing DRUG

COMPANY

INDICATION

ESTIMATED ANNUAL OR TREATMENT COURSE PRICE

Humira

Abbvie

Inflammatory Conditions

$50,000

Soliris

Alexion

Paroxysmal nocturnal hemoglobinuria

$440,000

Kalydecko

Vertex

Cystic fibrosis

$275,000

Naglazyme

Biomarin

Maroteax-Lamy syndrome VI

$375,000

Solvaldi

Gilead

Hepatits C

$84,000

Gleevec

Novartis

Multiple forms of cancer

$95,000 February/March 2015 BIOTECHNOLOGY FOCUS 13

Reimbursement Table 2: Forecasted Net Prescription Drug Spend %, Traditional and Specialty, For Commercial Plan Sponsors

are currently rare disease drugs and many market pundits don’t expect any significant pushback from payors in the foreseeable future.

Rare disease drugs continue to represent a relatively small portion of payors’ budgets, and these drugs treat high unmet medical needs in often vulnerable patient populations. Most importantly, there are usually no other treatments options for these patients.

Payors have the choice of reimbursing high prices, or letting patients suffer or even die.

True Innovation

Source: Artemetrx With the Abbvie/Express Scripts deal, the business plan from the payor side is clear: they are ready to give exclusivity, and therefore limit patient and doctor treatment options, for a discount.

And while many have scoffed at this kind of deal as disease specific - the argument is that Hepatitis C has a finite pool of patients providing an incentive to discount and grab market share - payors are making it clear that their intentions are to move into other disease areas.

The CEO of Express Scripts, George Paz, speaking at the J.P. Morgan Healthcare Conference in January, highlighted cancer and cardiovascular as two areas they could potentially use formulary exclusions to get discounted drugs.

What do Hepatitis C, cancer and cardiovascular all have in common? These diseases have new (and expensive) classes of drugs where price competition can be created. The greater the competition and the more similar the drugs, the more leverage payors have to exclude them for pricing reasons.

Some Areas Will Continue to Support High Prices As pricing pressure continues to mount in some areas, there are other drug classes that will be minimally affected or not affected at all. These are the areas that drug development companies should be focusing on, and where investors will see strong returns.

Drugs with strong pharmacoeconomic data that quantifiably reduce healthcare costs will continue to drive high pricing.

Even in the case of Sovaldi – Gilead’s HCV drug - most payors reimbursed it because the pharmacoeconomic data was strong.

For example, using the drug resulted in a significant reduction in hospitalization and the need for expensive surgeries for hepatitis C patients. And while this component is so important to pricing, it’s amazing how many companies continue to run Phase 2 and even Phase 3 studies without collecting parmacoeconomic data.

Rare Disease Drugs The highest priced drugs on the market

Table 3: Payors Other Drug Utilization Management Tools Step Edit

Patient must fail other less expensive therapies first

Prior Authorization

Require authorization based on proper diagnosis

Co-insurance

Require patient to pay certain percentage of drug cost

Pay for Performance Pay for drugs further to successful pre-determined patient outcomes Quantity Limits

Limited number of prescription refills

14 BIOTECHNOLOGY FOCUS February/March 2015

Too often, drug developers have tried to price high with little innovation. These aggressive pricing strategies include certain reformulations that may increase patient compliance, or drugs with incremental benefit.

The pricing of these drugs could come under serious pressure in the future. A widely mediatized example is Sanofi’s Zaltrap, a cancer drug whose price was halved after doctors refused to pay the $40,000 price because they considered lower-cost options just as effective.

The other side of this is that meaningful innovation should and will continue to get rewarded with high pricing.

True breakthroughs are those that provide significant leaps from current standard of care, or treat diseases where patients have no options. Wall Street is currently modeling pricing for the potential CAR-T immunooncology cancer therpapies in the $350,000 range and similarly for the gene therapy treatments that are being developed at companies like bluebird bio. That pricing range is likely not far off the mark.

Healthcare systems around the globe are under pressure to reduce costs. Needless to say, drug companies have a role to play even if forced to in certain circumstances - to keep costs in check.

Payor pushback and pricing in general are key factors that feed into drug development and investor decision making. Following the correction in December, the NBI has reached new all-time highs in January. It seems that investors agree - the prospects of new therapies in areas of continued strong pricing outweighs the risk of payor pushback.

Roberto Bellini is the President and CEO of BELLUS Health Inc. To see this story online visit www.biotechnologyfocus.ca/ specialty-drug-pricing-worthrisking-payor-wrath

By Joanne Koskie and Christine Beyaert

Orphan Drugs

It’s not easy being rare An estimated 2.8 million Canadians live with one of the more than 7,000 identified rare diseases. For many there is little relief, but for a select few who suffer from one of these disorders, treatments are available – if they can get access to them.

T

he issue of orphan drug reimbursement by public payers has become central to companies that develop these innovative therapies and the patients who need them. Orphan drug research and development costs are amortized across a small patient population, so a drug’s economic viability rests on a relatively higher per-patient price. As a result, most patients cannot afford to pay for these treatments themselves, instead relying on public or private coverage.

While our healthcare system is considered among the best in the world, Canadians with rare disorders are at a marked disadvantage when it comes to accessing treatment. Only half of the rare disease drugs available to patients in the U.S. or Europe are approved in Canada, and only half of these are funded by public drug plans. Those recommended for funding are often met with restrictive criteria and conditions, further limiting patient access.

It is by no means easy being rare, but orphan drug reimbursement is achievable – even in the most challenging situations – through a strategic, integrated approach to communications.

Price, policy and political will Drugs for rare diseases face unique and seemingly unsurmountable challenges that impact funding decisions, including the cost of treatment, health technology assessment policies and low political will. In any effort

to gain reimbursement, these barriers must be addressed and overcome to ensure patients have timely access to life-transforming treatments.

Several orphan drugs approved in the past few years have seemingly hefty price tags, with some in the million-dollar range per patient, annually. Research and development costs, and the associated high risk, are not well understood or widely accepted and are overshadowed by sticker shock. While the price per patient is high, the few approved drugs for rare diseases in Canada consume less than one per cent of the total spent on pharmaceuticals. Further, these drugs can alleviate downstream pressure on the healthcare system, by contributing to a reduction in doctors visits, hospitalizations, surgeries and disability.

Representing another significant hurdle, health technology assessment (HTA) processes that evaluate and make funding recommendations for new treatments are virtually the same for rare disease drugs as for other medications. Many orphan drugs are not recommended for reimbursement because the evaluation criteria – safety, comparative clinical-efficacy, and comparative cost-effectiveness – have not been adapted to the unique characteristics of rare diseases.

Since these treatments are firsts, there are no benchmarks to gauge cost-effectiveness.

While efforts are made to incorporate patient, caregiver, and health care provider

input, drugs for rare disorders remain at a disadvantage because current HTA processes prioritize cost containment over making treatments available to patients who desperately need them.

Policy issues are compounded by fiscal constraints with provincial and territorial healthcare budgets under constant scrutiny.

Policymakers responsible for those budgets are under pressure to reduce costs while maximizing the public interest. Political will is influenced by the intensity of public sentiment and how closely a particular issue intersects or aligns with the agenda of the day.

Thus, governments are responsive to the files that most urgently demand their attention.

If only a few people in a province require a treatment, their voices may be difficult to hear. There is little benefit for governments to respond to the demands of small patient groups. In some cases, what dominates is the perceived risk that voters will see the opportunity cost to treat a single patient with a rare disease as simply too high.

Making rare roar by strategically integrating communications Successful reimbursement efforts necessitate a multi-stakeholder, multi-channel approach that strategically integrates advocacy with government and media relations. Moreover, the process of building and sharing the social and emotional value story for treatment February/March 2015 BIOTECHNOLOGY FOCUS 15

Orphan Drugs

Access to orphan drugs can have an undeniable life-changing impact on those patients who are fortunate enough to receive treatment, but come at a high cost in terms of invested time and energy.

needs to begin long before a rare disease drug is market-ready. The unmet clinical need must be established, and accepted by payers and the public, before the solution is available and access is sought.

Patient-focused messages Unfortunately, Canadian reimbursement processes for rare disorder drugs currently favour economic analysis over clinical data, making the need for the patient and physician voice even stronger. Regardless of the per-patient cost, treatment outcomes are arguably priceless. These therapies represent the first and often only treatment for a condition that is often progressive, life-shortening or imminently life-threatening.

Reimbursement objections need to be addressed through messages that speak to the clinical significance of the drug from the patient perspective and that of the medical expert, framed in a way that resonates with government and the public. Without a clear understanding of how a treatment can transform lives, the clinical data and impact of the drug on quality of life is at risk of being overshadowed by price.

The patient and physician voice are particularly important as they underscore the real-world impact of a medication that affects so few lives. Clinical experts can put the costs and benefits of a rare disease treatment into perspective, lending credibility to an otherwise emotional appeal. By sharing their personal stories and unique perspectives, patients and caregivers can very effectively make the personal political, and provide insight into the data that the public can identify with, even if they aren’t touched by the disease.

Expanded support base Communication efforts are critical in rare disease advocacy as many disorders are not widely known and receive little visibility.

Initiatives that serve to amplify the patient 16 BIOTECHNOLOGY FOCUS February/March 2015

voice and broaden the base of support will succeed in influencing public opinion and ultimately, the political agenda.

It is essential to engage the core group of stakeholders – people living with the disorder, their friends and families – and help them to unite and mobilize. This natural base of support is especially important because advocacy relies on volunteers who often have limited time, funds, and expertise. Further, the people directly impacted by a lack of access to treatment are often consumed by battling their disease, or taking care of a stricken loved one.

The power of engaging personal networks cannot be understated. While a rare disease drug may only treat a handful of people, its impact extends to families, friends and communities. The ultimate goal is to expand engagement beyond personal networks to the broader public in the hope that they will identify with their plight. Encouraging patients and their families to tap into their networks can build the critical mass necessary to apply sufficient political pressure.

Expanding the base of support requires engagement on many platforms – in person, online through a variety of social media channels, and through traditional print, radio, and television media. It is important to recognize that today’s world is visual and fast-paced, and to tailor efforts to the medium. The message needs to grab someone’s attention within 15 to 30 seconds, which makes compelling images, videos, and personal pleas even more important.

Taking an integrated approach An integrated approach to advocacy campaigns is a critical component in influencing and driving change. Given today’s rare disease drug reimbursement landscape where political pressure is almost always required, public relations and public affairs are inextricably linked. It is not enough to simply meet one-on-one with government officials or to tell your story to a reporter – the two must go hand-in-hand and be leveraged through social platforms.

To even consider taking action, decisionmakers need to hear messages repeatedly

from multiple credible sources, through a variety of channels. The Internet and social media have made the world smaller and the opportunities to foster connections through communications much easier. They provide advocates with more ways to engage with government and the general public, but they also demand consistent messaging and persistent action.

Hope for change The challenges surrounding public reimbursement for rare disease drugs are considerable, the stakes are high, and much needed policy changes are very slow to come. Often, rare disease patient groups are neither expecting nor prepared for the fight they are certain to face. Access to orphan drugs can have an undeniable life-changing impact on those patients who are fortunate enough to receive treatment, but come at a high cost in terms of invested time and energy. Employing a strategic approach to market access that integrates advocacy with government and media relations has demonstrated effectiveness in bringing treatments to patients sooner by encouraging positive drug funding decisions. There is hope – at least for small changes – when the power of the patient and physician voice is brought to bear.

Joanne Koskie, Vice President, Cohn & Wolfe, brings two decades of communications experience as a consultant and within the voluntary sector. Joanne supports the work of dozens of patient groups, providing strategic leadership and direction on integrated, nationwide advocacy campaigns for access to care and treatment. Christine Beyaert, Counsellor, Cohn & Wolfe, provides an insider’s view on public relations from within government and the patient community with a focus on social and digital communications.

To see this story online visit www.biotechnologyfocus.ca/ easy-rare

INTELLECTUAL PROPERTy

personalized medicine

patentIng controVersIes By: Carmela DeLuca and Katherine Bonter

Whether diagnostic and personalized medicine technologies or “gene patents” should be the kinds of inventions that can be patented (e.g. whether they are patentable subject matter) has been under scrutiny in a number of jurisdictions and the potential commercial implications hotly debated. Court challenges have been ongoing in Australia and the U.S. and most recently launched in Canada, bringing the controversy to our back yard.

H

ere the current state of patent protection in these jurisdictions is explored by comparing and contrasting recent court decisions and the existing legislative environment.

United States Exemptions to patent subject matter eligibility, as expressed by the U.S. courts, include: fundamental principles, laws of nature, natural phenomenon and abstract ideas, the building blocks of human ingenuity.

Judicial exemptions are intended to prevent patents from broadly pre-empting or tying up the use of fundamental ‘building blocks’ and to restrict patents to inventions that are a “product of human ingenuity” (35 USC §101). Recent U.S. Supreme Court decisions have considered if certain inventions involving: a law of nature (Mayo 2012)1, a natural phenomenon (Myriad 2013)2 or an abstract idea (Bilski 20103 and Alice 20134) are patFebruary/March 2015 BIOTECHNOLOGY FOCUS 17

Intellectual Property entable. Responding to these decisions, in particular to the 2013 decisions, the USPTO is implementing major changes to how examiners evaluate claims that recite a judicial exemption.

Three examination guidance documents were recently issued by the office: “Guidance For Determining Subject Matter Eligibility Of Claims Reciting or Involving Laws of Nature, Natural Phenomena, & Natural Products” (March 2014), “Preliminary Examination Instructions in view of the Supreme Court Decision in Alice Corporation Pty. Ltd. V. CLS Bank International, et al .”

(June 1014) and “2014 Interim Guidance on Patent Subject Matter Eligibility” (December 2014).5 The March 2014 was strongly criticized by many stakeholders. After formally receiving and considering this criticism6 the December 2014 guidance was issued, replacing the earlier guidance.

According to the December guidance, examiners will apply a three step process: (1) is the claim directed to a process, machine, manufacture or composition of matter, if yes (2) does it recite or describe a judicial exemption and if yes (3) does it recite additional elements that amount to ‘significantly more’ than the judicial exemption.

In determining if the invention claimed is ‘significantly more’ examiners are instructed to consider each claim element individually

and as an ordered combination (as a whole) and to identify structural or functional differences vs. the corresponding natural product.

For claims that recite a natural product, evaluating ‘significantly more’ involves consideration of structural or functional differences between the invention claimed and the natural product. One notable change, based on the USPTO’s interpretation of the Myriad decision, is that isolated biomolecules like peptides or oligonucleotides that are identical to segments of a larger naturally occurring biomolecule and having the same or a similar function to the ‘parent’ are considered as a natural occurring and not patent eligible. While the same logic can be extended to other types of biomolecules like antibodies, RNA or proteins where the therapeutic applications claimed derive from the natural function of the biomolecule, at present it is not clear how broadly this approach will be applied by the office.

Currently the extent to which DNA primers and probes will be patent eligible is not clear. The March 2014 guidance included an example of a specific pair of primers which was indicated as patent ineligible. Although this same example was removed from the December 2014 guidance, two days after the guidance was released, a Federal Court decision7 found broad claims to pairs of single stranded primers for amplifying the BRACA1

In December 2013, the High Court of Australia ruled that methods of medical treatment are patent eligible in Australia.

18 BIOTECHNOLOGY FOCUS February/March 2015

gene indistinguishable from naturally occurring DNA in both structure and function - not patent eligible. However, primers or probes conjugated to a non-naturally occurring label or moiety could be considered as structurally different from naturally occurring DNA and patent eligible under the current guidelines.

Regarding process claims that recite a natural product, the guidance provides an example treatment claim that indicates that such claims should be eligible if they are limited to a specific application e.g. clinical indication. As no example of a diagnostic method claim was provided, it is uncertain if diagnostic method claim that recites a natural product (e.g. oligonucleotide probe), or even multiple natural products, and concrete method steps, as opposed to abstract steps, will similarly be considered patent eligible.

As for diagnostic method claims that recite either one or a combination of correlations between a biomarker and a clinical phenotype (a natural association) little guidance is provided by the current guidelines as to what will meet the requirement of significantly more.

Australia On September 5, 2014, the full bench of the Federal Court in a unanimous decision upheld a lower court decision that found that isolated nucleic acids are patentable subject matter. The challenge had been launched

by Cancer Voices Australia and breast cancer patient, Yvonne D’Arcy, against patents owned by Myriad Genetics. Similar to the U.S. case, one of the patents challenged claimed isolated nucleic acid sequences coding for the BRCA1 gene which has been linked to breast and ovarian cancer.

The Australian test for patent eligibility includes assessment of whether the invention consists in an artificially created state of affairs’ that is of economic significance, meaning that its value to the country must be in the field of economic endeavour, and that it must have an ‘industrial or commercial or trading character’.8 Given this, a conclusion that isolated BRCA1 DNA is artificially created could be argued to follow logically. In December 2013, the High Court of Australia ruled that methods of medical treatment are patent eligible in Australia. Accordingly it would seem that patentability of diagnostic and personalized medicine innovations are on relatively solid footing in Australia.

An application with the High Court of Australia has been filed for special leave to appeal the decision of the full bench. A decision as to whether the High Court will hear the case is expected in the coming months.

Intellectual Property Isolated DNA is patentable subject matter and diagnostic claims that meet the other requirements of patentability are at present patentable subject matter.

Canada On November 3, 2014, the gene patent legal controversy spilled into Canada over patents relating to assessing risk of an inherited cardiac disorder, long QT syndrome.

The Children’s Hospital of Eastern Ontario (CHEO) commenced a patent proceeding against the University of Utah Research Foundation, Genzyme Genetics and Yale University asking for to a declaration of noninfringement and/or invalidation of a series of patents which claim isolated nucleic acids and methods of assessing a risk for long QT syndrome. It remains to be seen if this case will progress to trial, and if so what direction the Canadian courts will take.

In Canada, whether an invention is patentable subject matter is determined by statute and case-law. The Patent Act prohibits the patenting of “mere scientific principle or abstract theorem” and courts have decided that methods of medical treatment are nonpatentable10, although medical uses that do not require the skill of, or restrict, a medical professional can be patented. In late 2011 the Federal Court of Appeal rejected a test for patent eligibility being applied by the patent office11 and said that whether a claim is patentable subject matter is assessed by whether “the subject matter defined by the claim, [and not the contribution over the art] falls within the definition of “invention”.

Shortly thereafter the patent office released a draft guidance document for comment related to Office Practice Respecting Claims to Diagnostic Methods and Medical Uses. The document has yet to be made official and in the meanwhile, examination of diagnostic patent applications has been put on hold.

A practice notice on diagnostic claims is expected which will hopefully shed some light on how the patent office views the patentability of such claims

At present, the patentability landscape in Canada for diagnostic and personalized medicine innovations differs somewhat from that of the United States. Isolated DNA is patentable subject matter9 and diagnostic claims that meet the other requirements of patentability are also patentable.

One category of claims that the patent office has recently provided guidance on is medical use claims that rely on a diagnostic feature for novelty and non-obviousness. A document of examples was released on November 14, 2013 including analysis of a ‘personalized medicine’ claim. The claim - Use of a known compound X to treat a disease Y in a specific patient population having the gene mutation ABC - was found nonpatentable because it restricts the choices (skill) of practitioners on how to use X. This leads to the situation where a claim to a diagnostic assessment could be allowable but use of that same diagnostic assessment in a medical use claim would be not.

Patentability of diagnostic and personalized medicine technologies is an evolving landscape that will require attention to the country specific intricacies when trying to obtain meaningful patent protection. Although patent office guidance documents do not have the force of law, they do affect the examination procedure applied by the Office to patent applications and as such may limit the types of claims that are obtainable for personalized medicine innovations. However, the guidance will ‘evolve’ overtime based on: new court precedent, its application in practice by examiners and applicants successes in overcoming rejections. Gray areas should be clarified in this way going forward and strong pushback form applicants will be beneficial.

References 1. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S., 132 S.Ct. 1289, 101 USPQ2d 1961 (2012) 2. Association for Molecular Pathology v.

Myriad Genetics, Inc., 569 U.S., 133 S.Ct. 2107, 106 USPQ2d 1972 (2013) 3. Bilski et al. v. Kappos, 561 U.S., 130 S.Ct. 3218, 3231 (2010) 4. CLS Bank International v. Alice Corp. Pty. Ltd., (2013) 5. http://www.uspto.gov/patents/law/ exam/examguide.jsp 6. http://www.uspto.gov/patents/law/

7.

8.

9.

10.

11.

comments/myriad-mayo_guidance_ comments.jsp Myriad Genetics Inc. et al. v. Ambry Genetics Corp. United States Court of Appeals for the Federal Circuit, December 17, 2014 NRDC(1959) 102 CLR 252 at 275.

Monsanto Canada Inc v Schmeiser, 2004 SCC 34 at 22-24, and implicitly affirmed by the Supreme Court in Harvard College v.

Canada (Commissioner of Patents), 2002 SCC 76 In Monsanto, the Court held that a claim to a gene can be infringed through use without isolating the gene, even if the use occurs within a higher organism (at 77-78).

Tennessee Eastman Co v Canada (Commissioner of Patents), [1974] S.C.R. 111 Amazon.com Inc v Canada (Commissioner of Patents) 2011 FCA 328

Carmela DeLuca is a partner with Bereskin & Parr LLP and member of the Life Sciences practice group. Her practice focuses on patent matters, including advising on the management of patent portfolios in Canada and abroad, the preparation and prosecution of patent applications in the life sciences and the analysis of patent issues such as validity, infringement and freedom to operate. She also has experience advising on regulatory compliance.

Between 2010 and 2014, Katherine Bonter was Director of Promotion and Advocacy at CEPMED, a Centre of Excellence in Commercialization Research created and hosted by the Montreal Heart Institute (MHI). 2011, she has participated in the intellectual property (IP) capture and management activities at the MHI and its affiliate the Beaulieu-Saucier Pharmacogenomics Centre and is presently Director of Intellectual Property at the MHI. Katherine currently leads 2 projects that address research questions related to IP and innovation in personalized medicine, as part of large-scale genomics projects funded

by Genome Canada in 2012. Prior to coming to Cepmed, Katherine worked for 15 years in the biopharmaceutical industry in IP and business development, working for small-medium sized companies in the Montreal area.

To see this story online visit www.biotechnologyfocus.ca/ personalized-medicine-patentingcontroversies February/March 2015 BIOTECHNOLOGY FOCUS 19

By Durhane Wong-Rieger

Orphan Drugs

“The right drug to the right patient at the right time and at the right price.”

An Open Letter to Canada’s Health Ministers re:

Rare Disease Drugs

T

his is an open letter to all of the Heath Ministers in Canada from the Canadian Organization for Rare Disorders, presenting a simple and elegant solution to providing appropriate, timely, and sustainable access to therapies for rare disease patients and other targeted patient subgroups living with more common conditions.

Innovative therapies, including drugs for rare diseases, have been much maligned as threats to affordable drug coverage, but they may actually provide the solution to the ultimate goal of “the right drug to the right patient at the right time and at the right

20 BIOTECHNOLOGY FOCUS February/March 2015

price.” In order to use these “small patient population” therapies effectively and costeffectively, we need to evolve responsive and responsible pathways to manage their use. It is given that not all drugs work for all individuals. It is equally true that some drugs, albeit listed as “open access” on formularies, have demonstrated “more benefits than harms for only slightly more than 50 per cent of the persons tested.” So, for many common conditions, nearly half of patients may be prescribed a therapy that is individually suboptimal. Which, of course, is also not cost-effective.

Traditionally, clinicians wishing to pre-

scribe the right medicine and correct dosage would make their best guess (based on clinical guidelines), observe the outcomes, and adjust accordingly, or change therapies.

This is not a “common” pattern for rare diseases drugs, in part because knowledge about the disease, the therapy, and patient outcomes may be very limited, and there are few, if any, alternative therapies. In other cases, a “trial-and-error” approach (such as the “double-blind randomized controlled clinical trial”) is neither appropriate nor likely to yield illuminating results, since the therapy is designed specifically to address the “cause” of the condition, often a genetic abnormality, and the treatment (replacing a missing enzyme or blocking gene expression) almost always works. This latter scenario also defines “targeted” therapies (aka precision or personalized medicines) that are developed for subtypes of common conditions, often defined by specific genetic abnormalities (for example, gene mutations, changes in the DNA, and over-expression or under-expression of a gene). Again, once the patient is correctly diagnosed through the appropriate genetic and/or other tests, the therapy should work.

What may not be certain is whether all patients with the genetic abnormality require therapy, the optimal time for starting therapy, the potential complications of comorbidities, and the patient preference in considering the benefits versus risks.

A key barrier to optimizing appropriate and timely access is the lack of certainty around “real world” effectiveness, safety and patient timing due, in large part, to small and often short clinical trials. These are, after all, small patient populations often

Orphan Drugs with life-threatening or serious conditions and no other viable treatments where the goal has been to make therapies available, to the broader patient community, as soon as possible. Unfortunately, the short clinical trials, often using surrogate markers and a very narrowly defined sample to optimize results, is often the bane of the health technology assessors and payers, who are looking for certainty in clinical outcomes, changes in disease status, and/or additional “life years”, preferably high-quality ones.

This conundrum is a universal challenge, and various jurisdictions, including Canada, have evolved a variety of solutions. So what is the elegant solution that CORD proposes?

In 2014, CORD called for a “managed access” approach to drugs for rare diseases that would address both the urgent unmet needs of patients and the uncertainty of effectiveness and safety of drugs tested with small patient populations. In reality, managed access schemes, defined as “an approach to providing access to drugs by setting criteria (based on evidence) for starting (such as, disease status, symptoms, previous treatments, co-morbidities, or age), how patients should be monitored while on therapy, and criteria that would indicate the therapy needs to be changed or the patient transitioned to something else” have been used to introduce rare and targeted therapies for a number of years. For example, managed access schemes (aka as managed entry agreements, coverage with evidence development, or risk sharing schemes) underlie the Canadian Fabry Disease Initiative, Ontario’s Drugs for Rare Diseases framework, Cancer Care Ontario’s Evidence Building Program, and the first Federal/Provincial/Territorial “Expensive Drugs for Rare Diseases” proposal in 2008 as part of the National Pharmaceutical Strategy.

Currently, a limiting factor to MAS is the “disconnect” between the regulatory review (Health Canada) and all of the review processes (Common Drug Review, panCanadian Oncology Drug Review, Institut national d’excellence en santé et en services sociaux (INESSS), provincial drug reviews, and panCanadian Pharmaceutical Alliance) used to reach a decision whether to reimburse, or not. Similarly, the requirements for data and patient monitoring prior to allowing drugs on the market are mostly nonexistent once the drugs are in general use. The disconnect is driven partly by divergent aspirations: for patients and clinicians, the desire to access therapies matched to individual profiles, offering better efficacy and safety; for developers, managing the complexities and cost of proving targeted therapies for small patient

In Canada, the challenges of implementing managed access schemes have been (successfully) addressed with many of the rare disease drugs currently in use. populations; for payers, deciding value for money when drugs are very expensive and evidence highly uncertainly against traditional assessment methods. But that pattern is changing.

Canada’s imminent implementation of the Orphan Drug Regulatory Framework, premised on a lifecycle approach to drug approval, offers the opportunity to adopt a continuous evaluation approach that engages all stakeholders, including patients, reviewers, and payers, from the very beginning to define the “value proposition.” The collective goal is to define the desired outcomes from the each stakeholder’s perspective, set up mechanisms to assure the evidence is collected and analyzed, and to make evolving decisions accordingly (for example, update the guidelines, increase monitoring, liberalize access, or call for changes to the price).

In Europe, countries like Italy and Spain have been using managed access schemes, not exclusively for rare disease drugs, for many years. There have also been pilots in the UK and the Netherlands. In 2014, the European Medicines Agency announced the first set of drugs to be considered under its pilot “adaptive licensing” project, seeking “to examine whether iterative, ‘adaptive’ approaches to medicine development and authorisation offer advantages in terms of achieving the best balance between the need for timely patient access with the importance of providing adequate, evolving information on a medicine’s benefits and risks.”

As importantly, the project calls for early

engagement of the HTA bodies (under the umbrella of the European Network of HTA, or EUNetHTA), the payers, and the patient organizations to determine the evidence that needs to be generated as well as the “hurdles” to data collection.

Even in the U.S., where access and pricing have traditionally been negotiated through market forces, policy makers, publicly administered drug plans, and insurers are looking at a managed “health economics and outcomes research” (HEOR) approach to the reimbursement of precision medicines “when the clinical and/or economic value proposition for the broader patient populations is unfavorable, unclear, or unexceptional” as they seek to “limit coverage of such therapies to subpopulations most likely to benefit.”

In Canada, the challenges of implementing managed access schemes have been (successfully) addressed with many of the rare disease drugs currently in use. Rare disease clinics and specialty pharmacies have established patient registries (collecting natural history data along with drug utilization and other patient outcomes) and providing on-going monitoring and assessment, often updating clinical practice guidelines in the process. While recognizing the need for internationally linked MAS and patient registries, as well as international evaluation of outcomes, we suggest that Canada, at this time, take a bold step in implementing MAS as a standard strategy for “innovative targeted therapies.” The opportunity comes from Canada’s Orphan Drug Regulatory Framework (developed and soon to be implemented) and the recently announced Provincial and Territorial Health Ministers’ working group on “evidence-based approaches” to managing rare disease drug therapies. We urge the Working Group to set up pilot MAS projects with rare disease therapies currently seeking reimbursement to develop recommendations based on experience with real drugs and real patients. The Canadian Organization for Rare Diseases has asked that CORD be invited as a member of the working group to ensure the pilots and deliberations are directly informed by patient perspectives. We definitely can afford rare disease drugs. We cannot afford not to make them available. We just need to do right.

To see this story online visit http://biotechnologyfocus.ca/ open-letter-canadas-healthministers-regarding-rare-disease-drugs February/March 2015 BIOTECHNOLOGY FOCUS 21

Special Report

By Noel Courage, Bereskin & Parr LLP

Experimenting Without Infringing Patents Canada’s patent laws have a “safe harbour” exemption from patent infringement (s. 55.2(1) of the Canadian Patent Act). The safe harbour applies to activities reasonably related to generation of information for a regulatory agency, such as Health Canada or the U.S. FDA. The Canadian safe harbour is based on a similar provision in U.S. law, but the Canadian law’s wording is broader -- it is not limited to drug approval but could also apply to other types of regulatory approvals. There is also a common law exception to patent infringement which is created in court decisions, not statutes passed by the government. The common law exception is narrow, for example permitting testing of an invention merely to see if it works.

The narrow scope of this common law exemption was part of the reason for enacting the broader safe harbor.

Most of the recent court decisions were in the pharmaceutical industry. A leading Canadian decision, Merck et al. v. Apotex ([2006] FCA 323, Federal Court of Appeal), was made in the context of generic drug development.

In the Merck case, the Canadian Court held that Apotex prepared and tested the patented Lisinopril drug for the purposes of filing abbreviated new drug submissions necessary to sell lisinopril in Canada and the United States. Not all lisinopril data was referenced in Apotex’s submissions, but all data was directed to that purpose. Apotex also had stored samples in the event that they were required for future reference by the government. The Court concluded that the safe harbor was sufficiently broad to exempt these generic drug development activities from infringement. The safe-harbour can protect activities reasonably related to development and submission of information required by law, either before or after market approval. The Court also found that Apotex’s use of lisinopril in ongoing research and development of alternate formulations and alternate techniques for tablet-making fell within the common law exemption to infringement. This was because Apotex did not proceed beyond an experimental (testing) phase and were not take as steps to manufacture, promote and sell the product.

22 BIOTECHNOLOGY FOCUS February/March 2015

The safe harbour may not apply if the drug samples used for regulatory purposes are commercialized subsequent to their use for regulatory purposes. It is important to carefully keep records evidencing the regulatory purpose. In Apotex Inc. v. Sanofi-Aventis, 2013 FCA 186, since the generic company could not produce records showing the destruction of the disputed lots of drug clopidogrel, it was concluded that it had not demonstrated that the experimental and regulatory use exemption applied to those lots. Therefore, as a best practice, unused drug originally obtained for regulatory purposes should later be either producible or destroyed in a documented manner. This better practice was shown in a subsequent case, Teva Canada Ltd. and Apotex v. Novartis AG, 2013 FC 141. Apotex had carefully prepared evidence to account for all its test imatinib, and provided an undertaking to the Court that whatever is left over after the regulatory process is completed will be destroyed. In that case, the leftover material was not covered by the safe harbour, but could nonetheless be retained subject to the undertaking that it will be destroyed after reaching its expiry date.

There has not yet been a Canadian case in the context of innovative drug development (competing innovative companies), or use of a patented research tool, so there is still some uncertainty as to how the safe harbor applies in those situations. The safe harbor should have some applicability to the innovative drug development context because it was recently considered to be potentially available in the context of a mechanical device case involving two innovative competitors developing helicopter landing gear (Eurocopter v. Bell Helicopter Textron Canada Ltée, 2012 FC 113, aff’d 2013 FCA 219).

The Canadian safe harbour provides a useful tool for companies intending to do development for regulatory-related purposes in Canada. The boundaries of the infringement exception must be kept in mind, since any non-regulatory development, or change in character to commercial use risks infringement.

Ch

Cr

1

Children’s MiraCle network funds

14

Children’s

hospitals

aCross Canada

eaCh day, there are

4,900

Children

CritiCal priority needs for

who rely on the support of Children’s MiraCle network

MeMber hospitals in Canada

What is Children’s Miracle Network?

Children’s Miracle Network® raises funds for 170 children’s hospitals in North America, 14 of which are in Canada. These hospitals, in turn, use the money where it’s needed the most.

When a donation is given, it stays in the community, ensuring that every dollar is helping local kids.

These donations have gone to support critical research and training, purchase life-saving equipment, and ensure excellence in care - all in support of our mission to save and improve the lives of children.

Learn more at: ChildrensMiracleNetwork.ca

Across Canada

Searching for PROOF of

Person-Specific Prevention and Care

By Bruce McManus

Are diseases burdens or opportunities?

We are all too aware of the immense global burden of heart, lung and kidney failure, and the challenges they pose to communities, health systems, care providers, and patients and families. The impact of ischemic heart disease alone outstrips all other socioeconomic burdens in health, while not including diseases of the valves, cardiomyopathies, and developmental abnormalities. Chronic obstructive pulmonary disease, third in the world as a cause of death, is now second in the U.S. Other common conditions like asthma, pneumonias and various forms of environmental lung disease still plague people of our planet. The epidemic of dysmetabolism and obesity that now enwraps almost all societies is associated with a progressive frequency of renal disease and failure. Old-age associated dementias, ischemic brain diseases and cognitive impairment evoke fear for patients and great concern by architects of health care for the emerging 21st century.

Many of the risks and illnesses we face are termed “chronic” diseases. They do cast a shadow on health for years and in many instances for nearly a lifetime. Indeed, the roots of these “organ-based” conditions reside in the prenatal and perinatal periods and then evolve under the influence of environments, behaviours and genes over a lifetime. Yet, these chronic diseases are punctuated by episodes of acuteness and precipitant decline which lead to urgent care utilization and to cost-centre incursions underlying our painfully bloated healthcare budgets.

24 BIOTECHNOLOGY FOCUS February/March 2015

The enormity of the challenges in healthcare delivery cannot be overstated, but neither can the opportunities to make changes that alter the cost curve while improving quality of care and patient experiences.

Tools to identify people at risk with early disease, susceptible to rapid decline or unresponsiveness to various therapies are emerging. Better predictive, diagnostic and prognostic tests are now possible through the alignment and interrogation of multi-marker data sets that can represent the “system of health, risk or disease.” The PROOF Centre of Excellence resides at the eye of the storm in enabling a new era of laboratory medicine that supports better care for the many patients suffering from chronic diseases.

Can medicine really be more personal?

Personalized medicine shines before us like the Holy Grail. The term (or a poor variant like precision medicine) is used more and more – the right drug, for the right patient,

at the right time, in the right dose, at the right frequency – in a very pharmacotherapyconstrained context. However, there is much speculation on the promise of the molecular genetic approach alone to render widespread, person-specific prevention and care.

The essential inclusion of high quality data and information regarding environmental influences (physical, ethnic, social, economic, educational, therapeutic, etc.) and behaviours (diet, physical activity, stress reduction, substance abuse, medication compliance, etc.) is often taken for granted or ignored in the rush to think about genes. Humans are not locked in cages, do not have standardized light-dark cycles, did not come from the same genetic stock, and have widely variant journeys that modify their gene expression, their regulatory systems and their responses to stimulation or injury. With these caveats, and while truly personalized medicine is currently less rather than more common, even in the most advanced societies, we are seeing great strides, especially in areas such as

Dr. Dan Holmes and Grace van der Gugten of the St. Paul’s Hospital Clinical Laboratory work hand-inhand with the PROOF Centre team to validate new blood tests for clinical care.

& s& bs ub e pu ve op tiiv to ut et cu se ec os xe lo e c ex cl

S RESTO

S UI TE

S

e he th ot to st ns miin 2 2m

Y SWA QUEEN

dehin gs b n i nly t ee as o y! ft m e le nw a

Howntowocks aw d l wb A fe

THE

SURPRISING DOWNTOWN OTTAWA HOTEL YOU MIGHT HAVE MISSED.

377 O'CONNOR STREET, OTTAWA, ONTARIO

1-800-465-7275 WWW.VICTORIAPARK.COM

Really,

ReallyBig Hotel Suites.

The moment.You know it.

It happens any time you stay at a new hotel, right after you swipe your room key. The moment before you open the door. Will the room be big, or small? Light, or dark?

Nice, or not?

and feature real bedrooms, real kitchens and real living rooms. And they don’t cost any more than those of our competitors. Really, why would you stay any place else?

Here’s what you’ll find the moment you open your door at Albert at Bay—space, and lots of it. Our suites are the biggest in Ottawa

DOWNTOWN OTTAWA

435 ALBERT STREET

613.238.8858

RESERVATIONS 800.267.6644 ALBERTATBAY.COM

Across Canada biomarker development, pharmacogenomics, and oncogenomics—inching towards a more tailored approach to health care.

Personalized medicine will not be achieved in a basic laboratory, by a government, through a private corporation or as individuals alone. If there is anything we have learned on this first leg of the journey, it is that we must build on the potential of diverse teams, knowledge and resources to truly achieve anything of pervasive and lasting value. Humans and their societies are complex, so we know that the solutions will not be immediately simple in production or implementation. Tapping the value that resides in a full range of sectors has become a maxim for success. Others like Drs. Federica Raia and Mario Deng would say that we need to consider the entire interface between new technologies and human beings, what they define as Relational Medicine in order to be truly effective in an era when technology appears to dominate our lives as patients or caregivers.

What has the PROOF Centre learned that we bring to the table?

In the Centre of Excellence for Prevention of Organ Failure (PROOF Centre), teams are developing high-value biomarker-based blood tests for improved patient management, especially those with heart, lung or kidney failure. A world-leading analytics team in the PROOF Centre is harnessing the power of clinical, molecular and computational data and nuances to move laboratory medicine into a new dimension of impact for patients and their caregivers. Health economists are providing essential and rigorous guidance on questions of value and in the development of decision support tools that can help to assure better tests and make them more useful.

Similarly, outcome collaborators are poised to assess the impact of new tests along the life cycle of organ failure on patients, their families, caregiving and the healthcare system itself.

PROOF Centre’s core strengths relate to critical guidance by expert clinicians regarding unmet needs in clinical management that could be addressed by a new generation of sensitive and specific blood tests. The multimarker tests are reflective molecular science of human biology and its systems, are generated by a layered data analytics strategy, and draw scientists, practitioners, and trainees to the challenge that extends across all disciplines, sectors and geographies. Together this team harnesses all relevant perspectives necessary to mature and implement new 26 BIOTECHNOLOGY FOCUS February/March 2015

Dr. Raymond Ng, Chief Informatics Officer, PROOF Centre, and computational team use systems science tools and data analytics to develop new biomarker signatures as blood tests blood tests. Such tests are driven by the desire to prevent disease or catch it early in an accurate fashion, and to enable physicians and their teams, whether they practice in primary or quaternary care settings. Such a thrust is also influenced greatly by patient needs and comforts. Tools to accelerate and make drug discovery programs of the pharmaceutical industry more efficient are also front and centre. Thus, the development of companion diagnostics or providing support for more efficient drug development pipelines, including cohort enrichment and patient population stratification, are among our day-to-day objectives.

By brief examples, the team, in strong collaboration with physicians and scientists of Alberta Heart and Dr. Ignaszewski locally, is working on new tests to correctly and more quickly identify patients as having chronic heart failure than possible now without imaging at regional or quaternary centres. Such blood tests, as well as those to identify different subtypes of chronic heart failure and to monitor patients for recovery of heart function from drug therapy, will improve care. For acute heart failure patients, teams including Dr. Anson Cheung have identified biomarkers that predict outcomes such as survival and response to mechanical circulatory assist device therapy. These tools are expected to lead to better patient care through appropriate targeted therapies.

With many collaborators, especially Dr. Don Sin, the PROOF Centre is also committed to develop new blood tests to manage COPD patients, hopefully reducing their need to

access urgent care through early recognition of their individual risks of acute exacerbation (lung attacks). We are similarly intent on helping to forecast the rate of decline in lung function in COPD patients, which will improve patient management directly and in hastening drug development by industry.

In another example, the most advanced, the decade-mature Biomarkers in Transplantation program will render tests to be implemented at the St. Paul’s Hospital clinical laboratory for validation and real-time studies this year. This critical implementation step occurs through the expertise of Drs. Dan Holmes and Mari DeMarco, and with the collaboration of HTG Molecular Diagnostics, Inc. A majority of heart transplant patients could thereby ultimately forego the need from so many invasive heart biopsies during the first year post-transplant.

The PROOF Centre currently has developed blood test content for more than 15 indications in acute and chronic heart failure, chronic obstructive lung disease, asthma, chronic kidney disease, and heart and kidney transplantation. They also have major biomarker collaborations related to spinal cord injury and muscular dystrophy.

It is worth emphasizing once again that each biomarker program begins with understanding patients and their pressing clinical needs. The team works to develop clinically relevant diagnostic, prognostic and monitoring tests for earlier diagnosis and more effective and patient-friendly care of patients as well as guidance tools for the pharmaceutical industry. Blood tests are

Across Canada tailored to maximize patient benefit while led by those who achieve on the fly linkage of Bruce M. McManus MD, PhD, FRSC, FCAHS is reducing healthcare costs. The diversity and data sets in an ethics-enabling fashion. Whether a Professor, Department of Pathology and depth of the team mirrors the degree of dif- the scale of personalized medicine initiatives un- Laboratory Medicine, UBC, Co-Director, Inficulty in getting across the goal line with derway in jurisdictions like the United Kingdom stitute for Heart + Lung Health, CEO, Centre products. It is easy to get to the “red zone” can be matched here will depend on whether of Excellence for Prevention of Organ Failure with partially validated biomarker solutions, we can master data, locally, nationally and inter- (PROOF Centre) and Board Member, Personbut it requires everyone the field to score nationally.

Fortunately, patients are well on their alized Medicine Initiative (British Columbia). newon card:Layout 1 1/31/2013 9:09 AM Page 1 the touchdown. way to generating and immediately acting on Email: bruce.mcmanus@hli.ubc.ca their own data, recorded on wearable, mobile devices. Many will soon have their genomes Why is the future all about and what such at their electronic fingertips. As systems?

To see this story online visit From molecule to population, biomarker data is democratized, we must be nimble or inwww.biotechnologyfocus.ca/ development, for whatever end purpose, novation will pass by bureaucratically hampered searching-proof-person-specificdemands a systems attitude. In fact, it is a health sciences innovators like a roadrunner prevention-care systems within systems within systems within passes a stone. systems philosophy that is required. From DNA to protein, to metabolite, to cell, to tissue, to organ, to whole organism, to comSRC101 munity, to health system – all must be under consideration. Then, the fine art is taking that complexity and reducing it to signatures that define or relate to patient phenotypes and physiology in precise and accurate ways I wish to receive/continue to receive a complimentary subscription to for given risks and diseases. To achieve this Yes No BIOTECHNOLOGY FOCUS complete view, we need to embrace new Format Preference: print digital both tools and technologies; we need to not only think of the gene for example, but also the Signature:____________________________________Date: ___________________________ epigene; we need to think about biological Name:_________________________________Title: ____________________________________ networks, social networks, linkages among Company: ______________________________Dept: ___________________________________ medical disciplines, policy networks, engineering innovation, community designs, Business Address : _______________________________________________________________ and as Dr. Mark FitzGerald would remind City:_____________________________Prov: __________Postal Code: ____________________ us, about “humanomics”, the artful core of Telephone: ___________________________Fax: ______________________________________ health care. We need a truly systems apE-mail: ________________________________________________________________________ proach to developing new, powerful solutions to improve health and meet, face on, On occasion, BIOTECHNOLOGY FOCUS will send third-party information on products & services related to the lab and life science industries. These may be cancelled at any time. Please check here if you do NOT wish to receive these. the towering shadow of chronic diseases.

Can BC and Canada harvest their great opportunity in personalization of care?

Personalized medicine requires collaboration.

It especially requires enabling frameworks for data management. While there is understandable emphasis on “Big Data”, since there is SO much data within various resources, generated from such platforms as “Next Generation” sequencing technologies, yet there is simply a need to share data of all types and sizes in order for value to be realized in a timely fashion.

We are fortunate in Canada to have many data resources of direct pertinence to the efforts to improve health care. A number of these resources are national in scope. In BC alone, we host expert clusters and rich data sources. The Ministries are home to immense and potentially useful resources. While there are tools like Privacy by Design, a made-in-Canada solution for the challenges of data access and linkage, these are cumbersome, slow and still shrouded in fear. The future of healthcare innovation will be

JOB FUNCTION 50 C Level Management 50a Engineer 51b Principal Investigator / Research Scientist 51c Professor / Faculty 53a Group / Project Leader 53b Procurement / Supply Chain 53c R&D Director / Manager 54 Legal / Financial / Administration / Regulatory / Communications

55 58 59 60 62 63 64 65 99

Post Doc / PhD Student Professional Services / Consulting Lab Technician / Research Assistant Sales / Marketing IT Management Nurse / Practitioner Pharmacist Physician Other (Specify):

Academic Biotech Organization Clean Tech organization Contract Research / Manufacturing Organization 50d Diagnostics Organization 50f Food processing / manufacturing 50g Instrument Manufacturer / Distributor

50h Packaging / Distribution 50i Pharmaceutical Organization 50j Professional Services (legal, financial, consulting, recruiting, regulatory, communications) 52 Clinical Research / Hospital 53 Research Institute 55 Government Agency 99 Other (specify):

C86 Buying Influence A Authorize

B Recommend

A B C D E F G

Analysis Instruments Basic Lab Equipment Chemicals/Biochemicals Chromatography – Gas Chromatography – Liquid Filtration, Water Purification LIMS

H I J K L M Y

Liquid Handling & Sample Prep Microscopes, Optics, Cameras Safety & Hygiene Spectroscopy Testing Systems/Equipment Vacuum Equipment None of the Above

C88 Product Development Stage (check all that apply)

COMPANYs PRIMARY BUSINESS ACTIVITY 50 50a 50b 50c

C87 Which products are used in your lab?

C Specify

A Research/Development B Pilot/Scaleup

C Production/Manufacturing D Tech Transfer E Not applicable

C89 Are you building a new lab?

Yes

No

C90 We have the following enewsletters: 1 2 3 4

Biotechnology Focus eBulletin Laboratory focus eBulletin BioPharma BioMedical

5 Health Care 6 Agri-Food 7 Clean Tech 8 Industry Inte

For a quick response please fax: 905-727-4428 or e-mail: circulation@promotive.net February/March 2015 BIOTECHNOLOGY FOCUS 27

NEW PRODUCTS Chromatography Laboratories characterizing monoclonal antibodies (mAb) now have additional hydrophobic

Sample Collection Brooks Life Science Systems introduces the SampleStoreTM II SE, an extension of its SampleStore II automated storage solutions portfolio that can manage a wide range of consumable types. The modular SampleStore II SE solution is designed for libraries of 50,000 to 300,000 1.4 ml tubes at temperatures of -20° C to +20° C. It is scalable with expansion modules to meet future needs and can fit through

interaction chromatography (HIC) selectivity options, thanks to the expanded family of Thermo Scientific MAbPac HIC HPLC columns. The new MAbPac HIC-20 and MAbPac HIC-Butyl columns offer additional selectivity options for characterizing mAb oxidation variants, intact mAbs, mAb aggregates or fragments and antibody drug conjugates (ADCs). The new columns are also designed for compatibility with organic solvent and aqueous mobile phase, as well as for rugged stability and very low carry-over.

Web: www.coleparmer.ca Separation Solutions A completely new gel permeation/size exclusion chromatography (GPC/SEC) platform from Malvern Instruments breaks new ground for today’s analytical laboratories. Malvern’s innovative OMNISEC platform integrates highly efficient sample separation via the OMNISEC RESOLVE module and high sensitivity analysis using OMNISEC REVEAL, a fully integrated multi-detector array. The system

Web: www.thermoscientific.com Sample Measuring The Mettler Toledo MP50 Excellence is a flexible instrument for the automatic determination of melting points and melting ranges up to

a standard laboratory door. The system’s Strata™ user interface, used across all of Brooks’ automated storage systems, makes it easy to store and retrieve samples. The Strata software also enables comprehensive sample information management, scalability, and integration with laboratory information management systems (LIMS).

Web: www.brooks.com Peristaltic Pump Reduce setup time

300 °C. The instrument allows four samples to be measured simultaneously for higher efficiency. The intuitive one Click® colour touch screen provides fast and secure operation to the user. Accurate measurements are ensured thanks to temperatureaccuracy specifications and compliance with current standards including Ph. Eur., USP, and more. Visual camera observation and digital image analysis guarantee that the result values are reliable. The high resolution videos recorded during the measurement can be repeatedly played back on the instrument at any time. This allows you to check unexpected results by visually verifying the measurements.

Web: ca.mt.com 28 BIOTECHNOLOGY FOCUS February/March 2015

when pump head is opened while the unit is running. The pumps come with an intuitive keypad to quickly increase or decrease flow. View RPM on digital display for accurate control and repeatability. Purge tubing before and after use with reversible motor. For automated processes, remote control is standard. Catalyst FH100D Digital Peristaltic Dispensing Pumps display all operational parameters on the LCD for at-a-glance monitoring. Programmable dispensing modes include volume, time, or copy, with convenient programmed delay between cycles. These pumps can be programmed in seven languages.

with the Catalyst™ by Masterflex FH Series peristaltic pumps from Cole-Parmer. The integrated pump and drive systems arrive fully assembled and ready to run. Save additional time when changing tubing—30 seconds is all it takes. Tubing occlusion is automatic when the pump head is closed.

The interlock switch powers the unit down

Re

Ca so life

Don

ww

has applications wherever there is a need for detailed analysis and understanding of natural or synthetic polymers, proteins and macromolecules including the development of synthetic polymers, pharmaceutical and biopharmaceutical products and foods.

OMNISEC REVEAL includes the following four detectors: refractive index (RI), UV/ Vis Photodiode array (UV-PDA), low angle/ right angle light scattering (RALS/LALS) and viscometer. Its light scattering detector can accurately measure molecular weights as low as 200 Da or injection masses of 100 ng.

A new self-balancing viscometer design with a user exchangeable capillary bridge boosts instrument productivity and cuts lifetime costs by extending viscometer life, reducing instrument downtime and minimizing maintenance requirements. OMNISEC RESOLVE consists of a sample degasser, pump, autosampler and column oven, each optimized for precise, high resolution separations.

Web: www.malvern.com

Follow

Read it here first.

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

Don’t get left behind.

www.biotechnologyfocus.ca

Follow us on

@BiotechFocus

CALENDAR

FEBRUARY 2015

March 24-27 PharmaLink 2015 Venue: Cincinnati, OH Tel: 513-745-3020 Email: toombm@xavier.edu Web: www.pharmalink2015.com

February 25 BioContactQuebec 2015 Venue: Quebec City, QC Tel: 418 694-8778 Fax: 418 694-0614 Email : mgodbout@hodran.com Web: www.biocontact.qc.ca/

MAY 2015 May 4-5

February 27-March 1

Bloom Burton & Co. Healthcare Investor Conference Venue: Toronto, ON Tel: 416-640-7580 Email: bbloom@bloomburton.com Web: www.bloomburton.com/conference

BIOTECanada Investor Summit Venue: Whistler, BC Email: julie.mair@biotech.ca Web: www.biotech.ca

MARCH 2015 March 8-12

May 22-24

PITTCON 2015 Venue: New Orleans, LS Twitter: @Pittcon Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org

Labcon 2015 Venue: Montreal, QC Tel: 905-667-8688 Email: labcon@csmls.org Web: www.csmls.org

May 26

Venue: Toronto, ON Web: www.biotech.ca

JUNE 2015 June 13-17 Canadian Chemistry Conference and Exhibition Venue: Ottawa, ON Tel: 613-232-6252 Email: acampbell@cheminst.ca Web: www.csc2015.ca

June 15-18 Bio International Convention Venue: Philadelphia, PA Tel: +1.202.962.6655 Email: convention@bio.org Web: http://convention.bio.org/2015/

June 20-24 Canadian Laboratory Medicine Congress Venue: Montreal, QC Tel: 613-531-9210 Email: info@clmc.ca Web: www.clmc.ca/2015/

Vaccine Innovation Conference

Company & Advertiser Index COMPANY Page Website AlbertatBay.........................................................................................................25..................................................................................... www.albertatbay.com Amorfix Life Sciences Ltd............................................................................. 10....................................................................................... www.amorfix.com Bereskin & Parr................................................................................................ 11,22.................................................................................www.bereskinparr.com Best WesternVictoriaPark................................................................................25....................................................................................www.victoriapark.com Brooks Life Sciences.................................................................................... 28.........................................................................................www.brooks.com Caprion......................................................................................................... 9.........................................................................................www.caprion.com Children’s Miracle Network..............................................................................23................................................................www.ChildrensMiracleNetwork.ca CTI Life Sciences.......................................................................................... 11.................................................................................. www.ctisciences.com Dalton Pharma Services................................................................................ 9.......................................................................................... www.dalton.com EnGene Inc.................................................................................................... 8....................................................................................www.engeneinc.com Eppendorf...........................................................................................................32.......................................................................................... www.eppendorf.ca Life Sciences Ontario..........................................................................................7............................................................................ www.lifesciencesontario.ca MaRS Innovation........................................................................................... 7...........................................................................www. marsinnovation.com Merck Canada............................................................................................... 6.............................................................................................. www.merck.ca Mettler Toledo............................................................................................. 28....................................................................................................ca.mt.com National Research Council of Canada........................................................... 8...................................................................................... www.nrc-cnrc.gc.ca OncoGenex Pharmaceuticals Inc.................................................................. 10..................................................................................www.oncogenex.com Panasonic.............................................................................................................5.................................................. us.panasonic-healthcare.com/celliqseries POI Business Interiors.......................................................................................31........................................................................................................ www.poi.ca ProMetic Life Sciences Inc............................................................................. 6...................................................................................... www.prometic.com ProNAi Therapeutics Inc............................................................................... 6.......................................................................................... www.pronai.com Structural Genomics Consortium................................................................. 6............................................................................................www.thesgc.org Thermo Scientific......................................................................................... 28..........................................................................www.thermoscientific.com VWR.......................................................................................................................2......................................................................................................... ca.vwr.com Zymeworks.................................................................................................. 12................................................................................. www.zymeworks.com 30 BIOTECHNOLOGY FOCUS February/March 2015

media:scape™

furniture and technology merged to help teams access and share information www.steelcase.com/cometogether

expect more

Contact us to learn more

·media:scape™ creates a collaborative destination ·Everyone can share their digital information instantly ·Information is visible by all participants

POI Business Interiors has more than 50 years of experience in providing knowledge, products and services that help people work more effectively.

We understand the issues facing organizations today.

T 888 296 9967, F 905 479 6941 www.poi.ca info@poi.ca

Highly Evolved The advanced control station The BioFlo® 320 is the next generation in bioprocess control. Designed as a universal platform, the BioFlo 320 is capable of meeting the ever-changing needs of scientists in the biotech and pharmaceutical industries. The BioFlo 320 has the right combination of features to get the job done.

> Universal gas control strategy for both microbial and cell culture applications > Multi-unit control of up to eight systems from a single interface > Direct integration of digital Mettler Toledo® ISM sensor connectivity > Built-in optical pH sensing technology for use with BioBLU® vessels

For more information visit: www.eppendorf.ca/bioflo320 131.A1.0132.A © 2015 Eppendorf AG. Mettler Toledo® is a registered trademark of Mettler Toledo AG, Switzerland.

131.A1.0132.A.CA.15-BFO.indd 1

Full page journal ad Biotechnology Focus - BFO

1/28/15 4:43 PM