MedTech Dealmakers, October 2015

October 2015
medtechFrom the publishers of Nature
Dedicated to nurturing collaboration and partnerships in the medical technology industry
Medtech partnering: Megamergers and digital health
The realization of precision medicine
Demand for cancer technologies drives dealmaking
As originally published in the October 2015 editions of Nature Biotechnology, Nature Medicine
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FEATURES
M2 KEY DRIVERS IN THE MEDICAL TECHNOLOGY DEAL LANDSCAPE
Venture capital investment in devices remains lackluster, but megamergers and startups in
digital health, drug delivery and minimally invasive technology are providing new impetus
to today’s evolving medical technology industry.
M8 GENOMICS TECHNOLOGIES MARCH INTO NEW MARKETS
Next-generation sequencing platforms are building market share not only in the research
setting but also increasingly in population research and clinical applications.
M15 PRECISION MEDICINE’S INVIGORATING EFFECT ON CANCER
MEDICAL TECHNOLOGY
Global recognition and advances in precision medicine have led to new approaches in
cancer treatments and a consequent increase in dealmaking.
PROFILES
M4 LOHMANN & RAUSCHER
M5 BTG
M6 THE UNIVERSITY OF TOKYO
M10 NUGEN TECHNOLOGIES
M11 DNANEXUS
M12 INVIVOSCIENCES
M13 BIOCARTIS
M14 PACIFIC EDGE
M16 HISTIDE
M17 BIOPHARMA SNAPSHOT
October 2015
Dedicated to nurturing collaboration and partnerships in the medical technology industry
Medtech partnering: Megamergers and digital health
The realization of precision medicine
Demand for cancer technologies drives dealmaking
As originally published in the October 2015 editions of Nature Biotechnology, Nature Medicine
and Nature Reviews Drug Discovery as an advertising feature.
MedTech Dealmakers October 2015 cover.indd 1 10/09/2015 14:48

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medtechdealmakers www.nature.com/medtechdealmakers
Key drivers in the medical
technology deal landscape
Venture capital investment in devices remains lackluster, but megamergers
and startups in digital health, drug delivery and minimally invasive technology
are providing new impetus to today’s evolving medical technology industry.
AARON BOUCHIE
T
he first word that comes to mind when
thinking about recent dealmaking trends in
the MedTech space is ‘megamerger’. This
trend was epitomized by Medtronic’s acquisition
of Covidien for $49.9 billion in January 2015.
The new combined company is by far the largest
in the MedTech space, with more than 85,000
employees in 160 countries, $27.8 billion in rev-
enues in 2014 and $2 billion in R&D spending.
But that was not the only example of consolida-
tion in the top tier: Zimmer Holdings acquired
Biomet for $14 billion in June 2015, and Becton
Dickinson bought CareFusion for $11.7 billion in
March 2015 (Table 1).
Although the early-stage MedTech space
remains much smaller than biotech, companies
pioneering minimally invasive technology have
been spurring recent deal activity. Indeed,at least
19 of the 102 acquisitions during 2014 and the
first 6 months of 2015 were in this space. Two
other key developments in the space have been a
spurt of activity around drug delivery devices and
startups in the digital health space.
A consolidating industry
As is often the case when industries undergo con-
solidation among top-tier companies, increasing
the bottom line via cost synergies is a clear driver
of deal trends. Although such types of deals will
likely continue given the amount of cash the larger
MedTech companies have on hand, both large
and medium-sized companies also have shown
an appetite for smaller companies, albeit those
with marketed, de-risked, innovative products.
Medtronic, for example, spent billions to acquire
at least nine additional companies in 2014 and
the first half of 2015, all but one of which have
marketed products.
Elsewhere, other companies have been
refocusing their businesses on more profitable
sectors. Wright Medical, for example, has used
mergers and acquisitions to refocus its busi-
ness on biologics and on orthopedics products
for the extremities. According to Julie Tracy, the
company’s SVP and chief communications officer,
the upper extremity, lower extremity and biologics
markets are three of the fastest growing areas in
orthopedics. She believes that all of these areas
are underpenetrated and will continue to benefit
from product innovation. To achieve these ends,
in 2014 Wright unloaded its OrthoRecon hip and
knee business to MicroPort Scientific for $290
million and acquired OrthoPro,Solana Surgical and
Tornier. For $32.5 million plus up to $3.5 million
in revenue-based earn-outs, the OrthoPro deal
gave Wright numerous foot and ankle devices,
as well as some tissue grafts. Solana Surgical,
acquired for $90 million, provides numerous foot
bone implants and other musculoskeletal surgical
products. Wright’s largest deal was the $1.2 bil-
lion all-stock acquisition of Dutch company Tornier
NV. Billed as a merger, the deal granted Wright
shareholders 52% of the combined entity. Tornier
offers nearly 100 upper and lower extremity prod-
ucts for joint replacement, bone repair and soft
tissue repair,plus several biologics. Tracy said the
company expects to perform more acquisitions in
the future,but it is currently focused on closing the
Tornier transaction.
Such deals are taking place in a MedTech eco-
system that not only remains much smaller than
biopharmaceuticals but also has languished
in a prolonged downcycle for most of the past
decade as a result of poor returns,regulatory and
reimbursement challenges and limited access to
public financing markets. While the public markets
certainly opened in 2014 and the first half of 2015,
with 43 IPOs averaging $55.8 million, biotech's
numbers have still outshone MedTech's. Timothy
Haines, managing director at VC firm Abingworth,
says that the macro-economic environment is very
important to future trends in public investment.
Given the general attitude towards public equities
since the Chinese markets began tumbling this
summer,Haines believes that public investors may
soon find MedTech's low-risk,low-reward profile to
be more attractive than high-risk drug developers.
Innovation in the space has also been con-
strained by a limited number of active venture
funds, including Abingworth, Canaan Partners,
Domain, Lightstone Ventures, NEA, Orbimed
and Versant Ventures. In this respect, a positive
development in the area is the increasing influx
of cash into MedTech from corporate venture
funds. Whereas pharma companies’ corporate
venture funds have been an important source
of investment for biopharma startups for more
than a decade, MedTech corporate venture funds
have been few and far between. Haines says he
has seen more activity in this area, with larger
companies seeding new startups. For example,
Boston Scientific led a series A round of $5.9 mil-
lion for InterVene in March 2015. The startup is
developing a minimally invasive, catheter-based
approach to treat chronic venous insufficiency. The
technique creates new deep vein valves from a
patient’s own vein wall tissue, with aims of being
the first to correct the underlying cause of disease.
Even so, it is hard to see innovative startup
activity taking off in MedTech without more exit
opportunities for investors. Particularly in the con-
text of few IPOs, most venture capitalists (VCs)
are faced with a rather limited pool of buyers. This
pool includes such companies as Abbott, Boston
Scientific, CR Bard, GE Healthcare, Johnson &
Johnson, Medtronic, St. Jude Medical, Stryker,
Wright Medical and Zimmer. But with this small
selection, there is a restricted number of trade-
sale exits that can happen each year. Compared
with big pharma, there is also less impetus for
Table 1. Recent high-value MedTech mergers and acquisitions.
Date Headline Companies Deal value
(US$M)
January
2015
Medtronic buys Covidien PLC Medtronic PLC and Covidien PLC 49,900
June 2015 Zimmer buys Biomet Zimmer Biomet Holdings, Inc. and Biomet,
Inc.
14,000
March 2015 Becton Dickinson acquires
CareFusion
Becton Dickinson & Co. and CareFusion
Corp.
11,771
July 2015 St. Jude Medical buys Thoratec St. Jude Medical, Inc. and Thoratec Corp. 3,474
January
2015
EQT acquires Siemens audiology
business
EQT and Siemens AG, Siemens Audiology
Solutions and Siemens Healthcare
2,700
March 2015 Mallinckrodt buys Ikaria Mallinckrodt PLC and Ikaria, Inc. 2,300
September
2014
Danaher Corp. acquires Nobel
Biocare Holdings AG
Danaher Corp. and Nobel Biocare
Holdings AG
2,265
June 2015 Hill-Rom acquires Welch Allyn Hill-Rom Holdings, Inc. and Welch Allyn,
Inc.
2,049
March 2015 Cardinal Health buys Cordis Cardinal Health, Inc., Cordis Corp. and
Johnson & Johnson
1,944
May 2014 Smith & Nephew acquires
ArthroCare
Smith & Nephew PLC and ArthroCare
Corp.
1,500
*Data sourced from Informa’s Strategic Transactions (https://www.pharmamedtechbi.com/deals).

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system, for $250 million plus undisclosed
regulatory milestones. Also this year, Edwards
Lifesciences acquired CardiAQ, which is currently
recruiting patients for two clinical trials of its TMVR
system,for $350 million plus another $50 million
upon reaching a regulatory milestone in Europe.
The largest deal for minimally invasive technolo-
gies was Smith & Nephew’s $1.5 billion acqui-
sition of ArthroCare completed in May 2014.
ArthroCare develops and markets minimally inva-
sive surgical devices that incorporate its Coblation
RF technology. The company utilizes the technol-
ogy in its two major business segments, sports
medicine and ear,nose and throat. The Coblation-
equipped instruments operate at lower tempera-
tures than traditional RF-based electrosurgical
devices and lasers. As a result, they are able to
dissolve tissue in a less invasive manner,thereby
decreasing harm to surrounding healthy tissue.
ArthroCare also markets more traditional musculo
skeletal devices, such as knotless anchors, the
Opus AutoCuff suturing system, and PEEK (poly-
etheretherketone) and titanium anchors for hip
and shoulder labral repair.
Drug delivery technology
When it comes to alliances,drug delivery technolo-
gies have led the charge and are only increasing.
In 2014, there were 14 such deals, and 11 more
took place in the first half of 2015.
In the largest of these deals,in November 2014,
Intarcia Therapeutics granted Servier exclusive
rights to develop and commercialize type 2 dia
betes candidate ITCA650 worldwide (excluding the
United States and Japan). ITCA650 is a match-
stick-sized subdermal pump that delivers exena-
tide,a glucagon-like peptide 1 (GLP-1) agonist. The
product can be implanted via a five-minute in-office
procedure and needs to be administered only once
or twice each year. The drug-device combination
has completed three phase 3 trials and is cur-
rently in a fourth. Intarcia received $171 million up
front and is eligible for $880 million in milestones,
plus royalties ranging from the low double-digits to
the mid-30s. Haines believes drug delivery deals
will become increasingly important, particularly
when it comes to delivering larger molecules, cell
therapies and gene therapies.
In terms of innovation, substantial funding is
now being aimed at the intersection of drug deliv-
ery technology and what is known as digital health,
in which ‘smart’ tech converges with healthcare. In
June 2014,venture capital fund Canaan led a $32
million series A round for Chrono Therapeutics,
which is developing a drug–device combination for
smoking cessation. Chrono’s SmartStop is a wear-
able device that provides programmable, trans
dermal nicotine-replacement therapy in combina-
tion with real-time behavioral support. The device
keeps track of daily peak nicotine-craving patterns
and automatically varies nicotine levels throughout
the day to manage the cravings. Eliminating crav-
ings and withdrawal symptoms, rather than just
alleviating them, increases quit rates, according
to VC Brent Ahrens, general partner at Canaan.
Digital health
Apart from drug delivery, digital health is making
inroads in several other areas,such as consumer
health. The highest-profile deal in this area was
Novartis’s Alcon eye-care division’s collaboration
to develop Google’s “smart lens” technology,
which embeds noninvasive sensors, microchips
or other miniaturized electronics in contact lenses.
The partners are first developing a lens that meas
ures glucose levels in tears and transmits the data
to a wireless mobile device, eliminating the need
for diabetes patients to perform finger pricks
throughout the day. The companies’ second area
of focus is the development of a product that pro-
vides accommodative vision correction in the form
of a contact lens or intraocular lens for patients
with presbyopia.
Overall, according to incubator Rock Health,
venture funding for digital health companies
in the first half of 2015 reached $2.1 billion.
Five companies—Evolent Health, Fitbit, Invitae,
Mindbody and Teladoc—floated successfully on
the public markets.
Both Haines and Ahrens are very interested
to see what innovations come out of digital
health. But a big question remains: how regula-
tory approval and reimbursement environment
will evolve. Ahrens says that most VCs are able
to exit their investments in MedTech startups—
either by acquisition or by going public—only once
they have an approved product on the market,
and often only after they have established sales.
What has changed in recent years is the number
of device clinical trials required by the US Food
and Drug Administration, which is higher now
than it was in the past. Once a device is on the
market, companies also need to generate more
cost-effectiveness data in order to satisfy payors’
demands. The upshot is that VCs need to put
much more money into MedTech firms before they
see any returns,and the returns are often smaller.
For example, Canaan typically obtains 4× returns
in 6–10 years in MedTech companies, compared
with between 3× and 15× returns in about 4 years
for biotech investments, according to Ahrens. As
a result, MedTech startups will need to not only
have highly innovative technology to attract early
investors,but also understand how their products
will navigate and prosper in the regulatory and
payor worlds.
Aaron Bouchie is a freelance analyst, writer
and editor who covers the biotechnology,
pharmaceutical and medical device industries.
these large MedTech companies to look for innova-
tions,because they don’t face the same pressures
of immediate generic competition and patent cliffs.
One dark-horse buyer new to the MedTech space
is healthcare services company Cardinal Health.
Cardinal distributes pharmaceuticals and medical
products to hospitals,ambulatory surgery centers,
clinical laboratories and physician offices,in addi-
tion to operating the largest network of radio-
pharmacies in the United States. The company
expanded into the MedTech arena in April 2014
by acquiring AccessClosure for $320 million. With
the acquisition,Cardinal gained the Mynx femoral
artery sealing system and the Flash ostial system
dual-balloon angioplasty catheter for stent apposi-
tion procedures. In May 2015, Cardinal made its
biggest purchase, paying $1.9 billion for Johnson
& Johnson’s Cordis stent business. Cardinal also
entered the wound-management business by
acquiring Innovative Therapies and orthopedic
trauma–products manufacturer Emerge Medical.
Whether other healthcare services companies will
also take advantage of their distribution networks
to sell their own branded products remains to
be seen.
Of the remaining sectors that have seen signifi-
cant deal activity,one of the most active has been
minimally invasive technologies.
Minimally invasive technology
Interest in minimally invasive technology is noth-
ing new. Several years ago, Medtronic splashed
out $800 million on Ardian, a medical device
startup pioneering the approach of renal denerva-
tion. That approach involved a minimally invasive
endovascular catheter–based procedure in
which radiofrequency (RF) waves were aimed at
renal nerves with the aim of treating hyperten-
sive patients resistant to standard therapies.
Unfortunately, shortly after the acquisition, the
device failed to meet its endpoint in a pivotal
phase 3 trial. This not only sent shockwaves
through the sector but also curbed the appetite of
large companies for startups with experimental
and innovative products.
That relatively conservative attitude may now be
changing again. Donald E. Bobo, Jr., corporate VP
of corporate strategy and corporate development
for Edwards Lifesciences, notes that there is a
broad focus in MedTech on making procedures or
monitoring less invasive, either through catheter-
based approaches or through minimally invasive
therapies and technologies. Of 19 acquisitions
for minimally invasive technologies during 2014
and the first 6 months of 2015, 12 were for
products that accounted for the top two areas of
acquisition: surgical equipment and devices (7)
and cardiovascular (5) according to data from
Informa's Strategic Transactions.
In August 2015, Medtronic announced it was
acquiring Twelve for $458 million up front and
$50 million once the company’s transcatheter
mitral valve replacement (TMVR) device receives
CE-marking in the European Union. Abbott and
Edwards Lifesciences also have made large
acquisitions in the space in the past few months.
In September 2015, Abbott acquired Tendyne
Holdings, which is currently enrolling patients in
a clinical trial for its bioprosthetic mitral valve
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ADVERTISEMENT FEATURE
Lohmann & Rauscher GmbH & Co. KG
www.lohmann-rauscher.com
Advanced wound healing through partnering
Lohmann & Rauscher, a leading international provider of high-quality medical devices and
hygiene products for hospitals, medical practices and consumers for over 160 years, is looking
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Partnership ethos
L&R is an international family-owned company
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L&R has a very flexible approach to partner-
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CONTACT DETAILS
Katharina Merz,
Head of Innovation Management
Lohmann & Rauscher GmbH & Co. KG
Neuwied, Germany
Tel: +49 2631 99 6067
Email: katharina.merz@de.lrmed.com
BOX 1: FACTS ON POTENTIAL
PARTNERING OPPORTUNITIES
Key medical areas
Wound healing
Infection control
Hemostasis
Pain prevention, relief and control
Scar prevention and treatment
Regenerative/personalized medicine
Key technological areas of innovation
Ingredients and materials for wound care
products:
New materials, including biomaterials
Biocompatible materials consisting of
proteins, enzymes, cells and/or tissues
Next-generation antimicrobials with low
potential for resistance and toxicity
Antibiofilm agents for infection control
Medical technologies for wound care:
New medical technologies for all areas of
wound care
New applications for negative pressure
wound therapy
Diagnostics, sensors and biomarkers
for wound evaluation, preferably with a
subsequent treatment recommendation
Smart solutions
New therapy concepts
Holistic approaches, from diagnostics via
debridement to healing
New solutions should:
Be directly related to an indication and
provide a clear path to application
Have a target implementation of no more
than 5–10 years
Not be a pharmaceutical (although these
are not categorically excluded)

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BTG
www.btgplc.com
Driving innovation in interventional medicine
BTG combines medicines, device technology and new techniques to deliver more targeted treatments,
and is leading the way in bringing these innovative interventional medicine therapies to market.
I
mage-guided, minimally invasive
therapies are fast replacing traditional
surgical procedures and, where
appropriate, systemic drug treatments,
bringing many benefits to patients
and physicians. The trend is driven by
improvements in imaging technologies,
coupled with interventional medicine
techniques that use relatively small
access points into the body, such as a
minor leg incision to gain arterial access
or entry via the airways to treat a lung.
BTG is an international specialist
healthcare company with a growing
portfolio of innovative interventional
medicine therapies inspired by the needs
of specialist physicians and their patients.
“We have products in our portfolio that
really benefit patients, are important to the
physicians who use them and have a great impact
on clinical outcomes,” said Peter Stratford, chief
technical officer at BTG. “It’s that real focus on
what is important to patients and the physicians
who use our products that I think sets us apart
from other companies.”
Growing portfolio
Alongside BTG’s specialty pharmaceuticals and
licensing operations, interventional medicine
is now BTG’s fastest-growing business area.
Established through a series of strategic acquisi-
tions, the portfolio includes interventional oncol-
ogy, vascular and pulmonology products (Fig 1).
BTG entered interventional oncology in 2011
when it acquired Biocompatibles International
and its portfolio of embolizing and drug-eluting
bead products for the treatment of liver tumors.
TheraSphere, which comprisesmillions of glass
microspheres containing radioactive yttrium-90,
was added to the product line after acquisition
from Nordion in 2013.
BTG’s interventional vascular business also
grew in 2013 when the company acquired EKOS
Corporation and its EkoSonic Endovascular
System, which uses innovative ultrasonic accel-
erated thrombolysis technology to treat severe
blood clots and pulmonary embolisms. The
device complements BTG’s Varithena (polido-
canol injectable foam) product, launched in the
United States in 2014 to treat varicose veins.
More recently, BTG entered the emerging area
of interventional pulmonology after completing
the acquisition of PneumRx and its PneumRx
Coil in early 2015. This innovative treatment for
patients with advanced emphysema consists of
small shape-memory Nitinol implants designed
to tighten the airway network when placed in a
diseased lung.
Underserved patient populations
Together with physicians, BTG identifies the
unmet patient and physician needs that can
be met by novel, minimally invasive solutions.
It then supports these efforts with significant
investments to generate high-quality data
that enhance the potential of the new therapy.
In 2014, the company invested more than
US$100million in RD, over half of which funded
indication expansion and product innovation.
For example, since acquiring TheraSphere,
BTG has accelerated three phase 3 trials of the
product in the United States to support pre-mar-
ket approval (PMA) applications for advanced
hepatocellular carcinoma and second-line treat-
ment for patients with metastatic tumors in the
liver from colorectal cancer. There is also a fully
recruited phase 3 study in the United States to
support a PMA application for the PneumRx Coil,
as well as a pivotal study to support label expan-
sion of EkoSonic into the treatment of chronic
deep vein thrombosis and post-thrombotic
syndrome.
Once new therapies are approved, BTG mea-
sures endpoints such as patient quality of life
and cost-effectiveness, which are important
to payers and for physicians making a case for
their use within a hospital system. “We bring
real focus and an understanding of the interven-
tional medicine area, including how to work with
novel technology, how to generate the clinical
data and how to work with the payers and reim-
bursers, to make sure that those products are
successful,” said Stratford.
Importantly, BTG’s capabilities include
bringing drug-device combinations to market,
a process that can be complex from a regula-
tory perspective. “As the world of medicine
becomes more complicated, some things cease
to be easily characterized as either a
medicine or a device, and from that
point of view I think we are very well
placed,” said Stratford. Varithena,
for example, combines a propri-
etary microfoam-generating device
with a low (1%) concentration of the
sclerosing agent polidocanol and is
regulated as a drug by the US Food
and Drug Administration (FDA). It was
FDA approved in November 2013 for
patients with incompetent veins and
visible varicosities of the great saphe-
nous vein system.
Geographic expansion is another
growth driver for BTG; it recently
opened a regulatory and medical hub
in Hong Kong supporting expansion in
Asia, and established new direct-sales
forces in Europe and Taiwan. The company’s
bead product was recently approved in China.
Future opportunities
BTG is set to become a world leader in interven-
tional medicine therapies by 2021, and expects
to earn over US$1.25billion of revenue through
organic growth of the current portfolio. The
company remains open to relevant partnering or
acquisition opportunities, focusing on products
and expertise that complement its core areas
in interventional oncology, vascular medicine
and pulmonology. “In particular, we would seek
to acquire high-content technologies that offer
opportunities to maximize potential through
our unique capabilities,” said Charles Brigden,
head of business development at BTG. “We also
continue to seek opportunities to build our estab-
lished specialty pharma business.”
In return, potential partners can benefit
from BTG’s growing interventional medicine
sales force, regulatory capabilities and care-
ful approach to integrating the businesses it
acquires. “The benefit for the partner or acquired
company is that they retain the entrepreneurial
nature of their business and are able to realize
their ambitions, but with the support, resources
and infrastructure of BTG,” said Brigden.
CONTACT DETAILS
BTG Business Development
London, UK
Tel: +44 (0)20 7575 0000
Email: bd@btgplc.com
Figure 1: BTG has a growing interventional medicine portfolio
comprising interventional oncology, vascular and pulmonology
products.

The University of Tokyo
www.u-tokyo.ac.jp/en
The University of Tokyo:
leader in advancing innovation
Three collaborative platforms—a Center for Innovation (COI), a tripartite industry-academia group
(DUCR, TLO and UTEC) and the Translational Research Initiative (TRI)—showcase the University of
Tokyo’s commitment to the development and commercialization of new healthcare technologies.
I
n Japan, the national universities, including
the University of Tokyo, have long been at
the forefront of scientific and technological
research, but it was only with the passage of the
National University Incorporation Law, in 2003,
and the granting of independence to the national
universities,in 2004,that the universities started
developing strategic approaches to maximize the
returns on their research investments. With great
freedom and control over their intellectual capital
also came increased pressure and opportunity
for the universities to boost their role in shaping
technological development through all sorts of
collaborations with industry partners.
The University of Tokyo was quick in setting
itself apart by establishing a technology-transfer
organization in 1998 and then University of Tokyo
Edge Capital (UTEC), a venture capital fund that
invests in the university’s startups, in 2004 (the
firm currently manages assets with a combined
value of $250million). Both organizations are
headquartered at the University of Tokyo and
work together with the Division of University
Corporate Relations .
But in addition to getting directly involved in
advancing innovation through direct funding,
the University of Tokyo has become a catalyst
for early collaborations between academics
and industry, as exemplified by its Translational
Research Initiative (TRI), an interdisciplinary orga-
nization that facilitates drug development and is
a key player in large, multicollaborator, long-term
national research efforts such as the Japanese
Ministry of Education, Culture, Sports, Science
and Technology (MEXT) Center of Innovation (COI)
program, which brings together industry and aca-
demia to conduct challenging and high-risk basic
research that is expected to lead to commercial-
ization within 10 years.
The University of Tokyo is committed to advanc-
ing innovation at all levels and offers a broad
spectrum of opportunities for collaboration.
Open collaboration
In 2013, MEXT’s COI Science and Technology–
based Radical Innovation and Entrepreneurship
Program announced the first round of funding
for COIs in three ‘blue-sky’ research areas: (i)
health in an aging society, (ii) quality of life and
(iii) sustainable society. Each COI receives up
to ¥1.1billion ($9.2million) annually, for up to
9 years, to develop and manage a collaborative
effort among industry, university and government
in one of the three blue-sky areas.
The University of Tokyo was awarded two COI
programs—one on the ‘sustainable society’
track focused on the development of novel pho-
ton-centered research-and-manufacturing tech-
nologies at the Innovative Center for Coherent
Photon Technology, led by Makoto Gonokami,
current president of the university, and a second
in ‘health in an aging society’.
The latter COI, dubbed the Self-Managing
Healthy Society COI, has been tasked with devel-
oping a new self-managed healthcare system in
which elderly people improve their general health
and enjoy a high quality of life for a longer period.
To realize this vision, 33 principal investigators
at the University of Tokyo and 26 companies are
cooperating in the program (Fig. 1).
The director of the COI,Tomihisa Ikeura,was for-
merly a managing executive officer at Mitsubishi
Chemical Holding and has a strong background in
RD and corporate strategy–planning in a broad
range of business areas including chemicals,
polymers and healthcare. The deputy director
for business development is Chisato Nojiri, who
was a key player in the commercialization of the
world’s first maglev centrifugal pump–based
ventricular assist system at Terumo Corporation
and is currently a senior research fellow at the
graduate schools of engineering at the University
of Tokyo. The deputy director for research is Ung-il
Chung, a professor at the University of Tokyo
graduate schools of engineering and medicine.
A vision for healthy aging
Population aging and the social isolation of
elderly people that comes with it are on the rise
globally, and Japan is home to the most rapidly
expanding elderly population in the world1
.
One of the key contributors to the burden of
an aging population on healthcare expenditure,
and the social security system overall, is the gap
between life expectancy and healthy life span.
According to the latest data from the Japanese
Ministry of Health, Labor and Welfare, in Japan
this gap amounts to about 9 years for men and
almost 13 years for women.
The University of Tokyo’s COI on health in an
aging society is now applying an open-innovation
approach to combine a wide range of existing
and emerging technology assets at the university
and clinical resources of the University of Tokyo
Hospital to build solutions that could help reduce
the number of hospitalizations and outpatient
visits for elderly patients. For the industry part-
ners involved with the center, the program helps
de-risk their investment in innovative, early-stage
projects and provides them with an opportunity
to get first movers’ advantage on emerging busi-
nesses. Such an environment, with its emphasis
on open collaboration and public-private partner-
ship, fosters a targeted approach to developing
healthcare solutions for a sustainable world.
To fulfill its vision, the COI is prioritizing the
development of a platform related to medical
and healthcare information and communica-
tion technology that will provide individuals
with information and insights on their clinical,
healthcare and lifestyle history. Health-related
‘big data’ are gathered from individual clinical
records at the University of Tokyo Hospital,
medical check-up data, genomic profiles and
other lifestyle-related data streams such as
exercise and dietary records.
The goal of the platform is to help understand
asymptomatic and symptomatic stages of dis-
eases such as metabolic and locomotive syn-
dromes, cancer and dementia that affect the
quality of life of elderly people. In the case of
cancer, for example, the COI has started col-
lecting whole-genome clinical sequencing and
epigenomic information from patients to improve
early diagnosis and treatment.
The COI is also developing a portable device for
minimally invasive diagnosis of a range of condi-
tions to help shorten hospital stays and reduce
patients’ need for clinical access. Development
of devices for ultra-early diagnosis and for the
delay of disease progression is also under way.
Finally, the COI has established solid lines of
communication with Japan’s Pharmaceuticals
and Medical Devices Agency and National
“The next-generation
healthcare business to
support Japan’s super-
aged society cannot be
created by a single
company.
”TOMIHISA IKEURA, COI

Institutes of Health Sciences to streamline RD
and the regulatory path to ensure realization of
the vision of a self-managing, healthy, long-lived
society.
“The next-generation healthcare business to
support Japan’s super-aged society cannot be
created by a single company. Our COI, by making
the most of its ‘RD-Under-One-Roof’ system,
aims to greatly contribute to the development
of a new social system by enabling cooperation
across business categories,” said Ikeura.
Three-pronged innovation engine
To boost academia-industry relations and aca-
demic entrepreneurship, the University of Tokyo
has put in place a system that brings together
the Division of University Corporate Relations
(DUCR), the Todai Technology Licensing
Organization (TLO), and UTEC.
DUCR, established in 2004, supports the
building of strategic alliances with industries
and/or local governments, manages the uni-
versity’s intellectual property (IP) and fosters
entrepreneurship at the university through
consultation, incubation and education for
researchers and students. According to Toshiya
Watanabe, DUCR’s director general, “Based on
the University of Tokyo’s robust industry and gov-
ernment relationships, the university will further
leverage strategic alliances to boost entrepre-
neurship and strengthen IP management in order
to contribute to the improvement of society. We
hope that the University of Tokyo will function as
a key innovation ecosystem for society.”
The strategic alliance–building and entrepre-
neurship initiatives are conducted in coopera-
tion with Todai TLO and UTEC, both of which are
private entities associated with the University
of Tokyo.
Todai TLO, a subsidiary of the university that
was established in 1998, manages marketing
and out-licensing of the university’s technologies
in all fields. Technology licensing contributes to
industry collaborations and the establishment
of university-driven startup companies. In the
past 10 years, Todai TLO has entered into more
than 3,500 licensing agreements. Takafumi
Yamamoto, president and CEO of Todai TLO, said,
“Our role is to act as an agent for the university’s
researchers’ high-value IP. We offer a one-stop
service for interested parties to access IP belong-
ing to the University of Tokyo.”
UTEC, a venture capital arm of the University
of Tokyo, invests in startup companies spinning
out of the university and supports business
incubation of emerging technologies from the
university. Since its establishment in 2004,
UTEC has invested in 60 academia startup
companies through three sequential funds total-
ing approximately $250million; nearly 30% of
those companies are in the life science field.
To date this investment activity has resulted in
nine initial public offerings and eight merger-
and-acquisition exits.
“We will continue to support unique tech start-
ups globally through close cooperation with the
University of Tokyo and other top research insti-
tutes,” said Tomotaka Goji, president of UTEC.
DUCR, Todai TLO and UTEC support innovation
not only in biotechnology but also in other tech-
nology areas.
Found in translation
The University of Tokyo TRI is an interdisciplinary
organization set up to facilitate drug development
in an academic setting. Its overarching mission—
to translate basic research at the university into
practical healthcare applications—is achieved
through the gathering and mapping of informa-
tion about seed funding for drug discovery and
medical device development, with the organiza-
tion acting as a bridge between public and private
companies and providing consulting services to
develop strategies specific to relevant research
projects. A scientific steering committee consist-
ing of university faculty with pharmaceutical-com-
pany experience, RD and business development
representatives from pharmaceutical companies,
medical doctors, a patent attorney, representa-
tives from regulatory science and a legal adviser
helps TRI identify promising projects in the trans-
lational space at the University of Tokyo.
TRI, the COIs, DUCR, Todai TLO and UTEC pro-
vide the university with a unique edge, helping it
to further innovation in Japan and globally.
Masuhiro Kato, former president, CEO and
chairman of AstraZeneca, Japan, and currently
a project professor at TRI, said, “We have devel-
oped a very efficient translational research
system to support companies that seek new
sources of development and principal investiga-
tors that need strategic and practical advice to
guide their translational program. The University
of Tokyo possesses a wealth of outstand-
ing research achievements, yet many remain
rough diamonds. It is critical that through our
translational research system these diamonds
are turned into therapies and medical devices,
including in areas such as regenerative therapy.
It is our hope that you will consider University
of Tokyo’s translational research system to work
together on turning academic innovations into
clinical applications.”
Reference
1. Department of Economic and Social Affairs, Population
Division, United Nations. World Population Ageing 2013
(UN, New York). http://www.un.org/en/development/
desa/p op ulation/p ublic ations/p d f/ageing /
WorldPopulationAgeing2013.pdf (2013).
Figure 1: The University of Tokyo’s Self-Managing Healthy Society COI provides a forum for
stakeholders from academia, industry and government to discuss cutting-edge science and
technology and ways to improve quality of life in ‘super-aging’ societies.
CONTACT DETAILS
Hideaki Tojo, Project Senior Specialist
The University of Tokyo
Tokyo, Japan
Tel: + 81 3 5841 1383
Email: tojo.hideaki@mail.u-tokyo.ac.jp

ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENTM8
Genomics technologies march into new markets
Next-generation sequencing platforms are building market share not only in the research
setting but also increasingly in population research and clinical applications.
MELANIE BRAZIL
T
he first human genome cost $3 billion and
took 13 years to sequence; today such
an undertaking costs closer to $1,000
and takes only days, making large-scale genetic
analysis feasible and affordable. Short- and
long-read sequencers have become established
workhorses in biomedical research, and their use
is now expanding into clinical applications and
beyond. Most notably, the combination of high-
throughput genotyping with measurements of
other markers of health and disease is opening
up the area of precision medicine (PM).
Current research market
Over the past couple of years, Illumina, a global
specialist in genetic analysis technologies, has
introduced a broad portfolio of sequencers “that
has allowed the company to expand its leader-
ship position, build barriers to entry and accel-
erate the penetration of clinical markets,” said
Cantor Fitzgerald’s Bryan Brokmeier, senior VP of
equity research. “The company now has an esti-
mated 80% share of the ~$2.3 billion sequencing
market, which we expect to grow into the tens
of billions of dollars over the next decade.” The
company has seen record growth in the past
couple of years, fueled by sales of sequencing
machines, as well as companion reagent kits for
the hardware.
Thermo Fisher Scientific has the next largest
slice of the sequencing market share. It offers
two platforms; SOLid and Ion Torrent. Instead
of nucleotides, the SOLid system uses fluores-
cently labeled probes that are repeatedly ligated
to the lengthening strand, optically imaged and
then cleaved off. The Ion Torrent platform uses
unlabeled nucleotides on a semi-conductor
chip, which senses the release of hydrogen
ions when bases attach. Neither technology
has seriously threatened Illumina’s dominance
in the market; in fact, market share for these two
platforms shrunk from 2013 to 2014 according
to Genome Web.
The other major instrument providers include
Pacific Biosciences, Complete Genomics and
Oxford Nanopore Technologies. Pacific’s single-
molecule real-time sequencing technology
reports read lengths of more than 10,000 base
pairs. The long reads enable full characterization
of the complexity of intergenic DNA sequences.
In October 2015, Complete Genomics will launch
its first commercial product, the Revolocity
system, which is based on a two-adaptor,
300-base-pair insert and mate-pair sequencing
of 28 bases in DNA nanoballs. It offers end-to-
end sample preparation (genomic DNA, blood or
saliva), sequencing, analysis, automation and
workflow integration. In March 2013, Complete
merged with BGI-Shenzhen, after BGI purchased
Complete’s outstanding shares for $3.15 per
share. Complete continues to operate as a
separate wholly owned subsidiary.
Oxford Nanopore’s MinION, a device the size of
a USB stick, uses protein nanopores to sequence
single-stranded DNA, using changes in electrical
current to identify bases. In 2014, the technology
became commercially available, and in July 2015,
the company raised $109 million in new funding.
Elsewhere, Roche, after scrapping a partnership
with IBM in nanopore sequencing, got back in
the area, acquiring nanopore developer Genia
Technologies in a deal worth up to $350 million
including milestones and investing in another
startup, Stratos Genomics, which labels each
of the four bases with unique reporters that are
50-fold larger, thereby generating robust signals
in a nanopore-based detection system.
In the past year, these long-read technologies
have also been joined on the market by instru-
ments that convert short reads into synthetic
long reads. One example of this is Illumina’s
Moleculo; more recent examples are developed
by 10X Genomics and Dovetail Genomics.
Population sequencing
Although next-generation sequencing (NGS)
platforms have become an established tool in
the research arena, a highly anticipated area of
growth in the research market is the large-scale
genotyping of populations. In 2012, UK Prime
Minister David Cameron announced a project
to sequence the genomes of up to 100,000
people and use their genomic information in treat-
ment and studies of cancer and rare diseases.
The project, to be run by Genomics England, a
company established by the UK Department of
Health in July 2013, has contracted with Illumina
to provide the instruments and infrastructure for
sequencing and data analysis pipelines (this sum-
mer the company opened SeqLab, a service to
help labs new to population-based sequencing).
In June 2015, four companies were selected
to work on interpreting genomic data from the
first 8,000 patients participating in the project:
WuXi NextCODE for interpreting variants found
in individuals with both cancer and rare dis-
eases, Congenica and Omicia for rare-disease
interpretation, and NantHealth for oncology. The
study will last 3 years; if it is successful, Illumina
anticipates that it will lead to an expansion of
the effort to sequence a greater proportion of the
UK population.
In the United States, the White House
announced the Precision Medicine Initiative at
the end of January 2015. This initiative is some-
what similar to the Genomics England project, but
it plans to study the whole genomes of 1 million
individuals in order to improve health outcomes.
Several sequencing companies are seeing oppor-
tunities for growth as other governments begin to
PRECISION MEDICINE TOOLBOX
Next-generation sequencing platforms can answer questions related not only to the exome or
genome but also to the transcriptome and epigenome of any organism. Sequencing methods
differ in terms of how samples are obtained and the data analysis involved.
Whole-genome sequencing (WGS)
WGS detects the 3.2 billion bases of the human genome. The ability to sequence large cohorts
is now a reality, and WGS will enable deeper understanding of the regulatory and other features
in the human genome, as well as meaningful interpretations of whole genomes. WGS is also
important for agriculture and microbial genomes.
De novo sequencing
This method refers to sequencing of a novel genome for which there is no available reference
sequence for alignment. The quality of the data depends on the size and continuity of the gaps
in the data.
Whole-exome sequencing (WES)
WES captures only the protein-coding part of the genome. Representing less than 2% of the
human genome, WES is a cost-effective alternative to WGS. It is used for many applications,
including investigating genetic disease, population genetics and cancer studies.
Transcriptome sequencing
This method creates a biological snapshot of expressed genes by capturing RNA and converting
it to cDNA before sequencing. RNA sequencing can focus on mRNA, small RNA, noncoding RNA or
microRNA, depending on the steps included before cDNA synthesis.
Epigenome sequencing
Epigenome sequencing investigates heritable changes in gene activity caused by environmental
factors, such as DNA methylation and acetylation, DNA–protein or RNA–protein interactions, small
RNA-mediated regulation and histone modifications.

ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENT M9
head of Roche’s sequencing and tissue diag-
nostics units. He added that the company has
“diagnostics specialists involved in every project
in our drug discovery portfolio, searching for the
biomarkers needed for a personalized health care
approach.” In 2013, Pacific partnered with Roche
to develop, commercialize and license diagnostic
products for clinical use based on Pacific’s tech-
nology in a deal worth up to $75 million in up-front
and milestone payments. In 2015,in addition to a
majority share in Foundation Medicine costing $1
billion plus milestones, Roche bought Signature
Diagnostics, with the aim of using its blood
plasma and tissue oncology biobanks to develop
circulating cell-free DNA tests.
At the end of 2014, Roche acquired Ariosa
Diagnostics and its prenatal-testing portfolio.
The previous year Illumina had begun noninvasive
prenatal screening with its acquisition of prenatal
test maker Verinata. It also launched its VeriSeq
sequencing technology for pre-implantation
embryo screening. Many of the sequencing com-
panies anticipate growth in this market as their
platforms are expanded to average-risk women, a
market six times larger than the current high-risk
genetic defect market.
Growth has been relatively slow in the diag-
nostic space because businesses face some
serious headwinds in today’s legal, regulatory
and reimbursement environments. Diagnostics
has always been a low-margin business, and
resource-constrained payers are accustomed to
treating them like cheap commodities. What’s
more, many companies must provide clinical data
showing that a new diagnostics test contributes
to better clinical outcomes before reimbursement
is offered. All of this is in addition to an uncertain
regulatory future, even though the FDA recently
unveiled its controversial laboratory-developed
test guidance. As a result, companies such as
Foundation Health have built a substantial clien
tele in the pharma industry to hedge against
the difficulties of obtaining reimbursement and
approval for their tests.
Companion diagnostics and PM
Pharma companies are increasingly interested in
using sequencing in drug development, primarily
for oncology, although other indications are gain-
ing interest. Initially, pharma companies used
sequencing primarily for discovery, and mostly
outsourced the sequencing to contract research
organizations. As time has passed, instrument
providers, such as Illumina, and diagnostic com-
panies using sequencing, such as Foundation
Health, have increasingly pivoted their busi-
nesses to provide services to big pharma, par-
ticularly around companion diagnostics, which is
moving toward sequencing.
According to the Tufts Center for the Study of
Drug Development, 73% of cancer compounds
are now studied in the context of biomarker data,
and 42% of compounds across all indications
employ biomarkers. What’s more, investment in
personalized medicine is projected to increase
by 33% in the next 5 years.
In 2014, Thermo Fisher announced a partner-
ship with Nuclea Biotechnologies to accelerate
methods to quantify type 2 diabetes markers.
adapt population-sequencing projects like those
of the United Kingdom and the United States.
The interest in carrying out these population-
based studies has grown from clinical research
projects that have integrated sequencing into
trial design. For example, a multi-institutional
amyotrophic lateral sclerosis (ALS) sequencing
project at the New York Genome Center, funded
by the ALS Association and the Tow Foundation,
aims to integrate WGS data with other genome-
scale data, such as RNA sequencing data, to
understand the relationships among mutations,
gene expression and mechanisms of disease. In
August 2015, Biogen, the ALS Association and
Columbia University Medical Center announced
a new collaboration aimed at better understand-
ing how genes influence the clinical features
of ALS. This project, which currently includes
1,500 people with ALS, is the first to combine
NGS and detailed clinical phenotyping with the
hopes of ultimately enabling a PM approach
for ALS. According to David Goldstein, director
of Columbia University’s Institute of Genomic
Medicine, “It is likely that the most important
contribution of PM is not so much matching
patients with the right treatments, but rather
using the technologies of PM to create entirely
new avenues into understanding the basic biol-
ogy of disease and using that knowledge to
create entirely new points of intervention.”
Another project is the Alzheimer’s Disease
Neuroimaging Initiative, which since 2004 has
been validating the use of biomarkers and MRI/
PET for clinical trials and diagnosis in individu-
als with Alzheimer’s disease (AD). The initiative
involves an unprecedented policy for sharing pre-
competitive data access to increase the rate of
discovery. Plans to add whole-genome sequencing
(WGS) for 800 participants with AD will result in
the most comprehensive way of looking at AD yet.
These are just a sample of the type of human
research studies under way. They not only prom-
ise a continued growth in demand for sequencing
platforms but also have provided the groundwork
for what is perhaps the impetus for crossing the
rubicon to clinical practice.
Moving into diagnostics
Companies are going after the clinical sequenc-
ing market on two different fronts. First, they are
moving their instruments through US Food and
Drug Administration (FDA) clearance. In 2013,
the FDA cleared Illumina’s MiSeqDx system;
this helped spur record demand for the MiSeq,
including for both cleared and research-use-only
versions. Illumina and other sequencing compa-
nies have plans to obtain 510(k) clearance for
assays for sequencing platforms, primarily in
oncology practices.
Second, sequencing-based diagnostics are
also being developed. The two early growth mar-
kets are oncology (including cell-free DNA tests)
and noninvasive prenatal testing. Large pharma
company Roche is directly investing in the NGS
and diagnostics areas. “With capabilities in both
diagnostics and pharmaceuticals, Roche uses a
personalized approach to diagnose and treat vari-
ous cancers. Our diagnostic tools are also used
to help manage treatment,” said Dan Zabrowski,
The company has also entered into an agreement
with GlaxoSmithKline and Pfizer to develop a uni-
versal NGS oncology test for solid tumors that
will serve as a companion diagnostic for multiple
drug programs. A similar program in oncology
was announced in the same year by Illumina,
partnering with AstraZeneca, Janssen Biotech
and Sanofi.
Companies such as Stephen Fodor’s Cellular
Research are also using NGS and barcoding to
provide a sensitive single-cell genomics platform
that provides information on cellular hetero
geneity. Cellular Research published the results
of their work with this type of platform earlier in
2015; the company already has one confidential
large pharma interaction.
Challenges for the future
The real ambition of PM, said Goldstein, “is in
transforming the way we develop new medicines.”
He also believes that “other technological drivers
will be in genome editing and stem cell biology,
since they together create a clear pathway for
in vitro models of many human diseases.”
Many current challenges exist to further com-
mercial development of sequencing platforms,
including ensuring cohorts represent our nat
ural diversity, managing large consortia, ques-
tions facing drug regulatory agencies, grappling
with new technologies, shifts in intellectual
property protection, as well as physician and
patient education.
Genomics is helpful for determining predisposi-
tions and, in some cases, the utility of certain
drugs, but for the vast majority of clinical cases
and patients, it will be measurements of real-
time health status that will become central for
determining individualized treatment. Sam Sia of
Columbia’s Biomedical Engineering Department
and cofounder of biotech incubator Harlem
Biospace observed, “Technologies for monitor-
ing individuals’ health are becoming increasingly
available, especially with consumer electronic
devices moving into health measurements. The
devices currently measure mostly vital signs,
but it is inevitable they will move into blood tests
and portable imaging in the future.” Consumer
diagnostics provider Theranos has a commer-
cially available platform for cheaper lab tests
that can detect up to 30 conditions using only
drops of blood. The tests are offered through
retail pharmacies and are covered by a number
of payors.
What is clear is that NGS is already establishing
itself in clinical markets such as oncology and
reproductive health, in population research and in
companion diagnostics. But there are a whole
raft of underexploited opportunities yet to be
tackled, not only in understanding the role of
genetic variation in areas of human disease out-
side of cancer and childbirth, but also in animal
health, crop genotyping and breeding, infectious-
disease detection (including food and water test-
ing) and forensics, all of which suggest buoyant
commercial prospects for these technologies.
Melanie Brazil is the Chief of Staff, Precision
Medicine Initiative, at Columbia University,
New York, New York, USA

NuGEN Technologies
www.nugen.com
Accelerating genomics with advanced
sample preparation solutions
NuGEN Technologies provides scientists and clinicians with innovative and reliable
sample-preparation technologies for targeted genomic analysis and diagnostics.
W
ith the advent of fast, high-capacity
genomic-sequencing technologies,
scientists are gaining new insights
into the fundamental mechanisms of disease,
enabling doctors to analyze a patient’s genetic
makeup for improved diagnosis and personalized
treatment. But while next-generation sequencing
(NGS) platforms are having a major impact on
clinical research and diagnostic testing, use-
ful insights can only be gained if samples are
prepared for analysis in a reliable, unbiased and
reproducible manner.
NuGEN Technologies offers more than 100
sample-preparation products that allow labora-
tories and clinics around the world to efficiently
target and obtain useful sequencing data from a
broad range of samples, including those that are
limited in quantity, degraded or otherwise chal-
lenging to process.
In oncology, an understanding of the
molecular changes that drive an individual
tumor can lead to clearer diagnosis, treatment
and even monitoring for recurrence. Yet at each
step in patient care, tissue availability may
be very limited. NuGEN’s SPIA (single-primer
isothermal amplification) technology solves this
problem by using high-efficiency amplification
to enable expression analysis of very low-level
nucleic acid samples on both microarray and
NGS platforms. With SPIA, efficient sample
processing from fine needle aspirate (FNA)
samples is possible, in some cases eliminating
the need for more invasive biopsy procedures.
SPIA also enables the analysis of other limited
and/or compromised biological samples,
including laser-captured microdissections,
sorted cells, embryonic structures and formalin-
fixed paraffin-embedded (FFPE) samples. SPIA
is the core technology used in the Ovation Pico
WTA System for microarrays and the Ovation
RNA-Seq System V2 for NGS.
Blood samples, a potentially useful source
of gene-expression data in clinical trials, pose
a challenge because of the prevalence of
hemoglobin RNA. Insert Dependent Adaptor
Cleavage (InDA-C) is a NuGEN technology that
uses a targeted approach to deplete unwanted
high-abundance transcripts during sequenc-
ing library construction. InDA-C substantially
reduces the number of sequencing reads
that are derived from the high-abundance
RNA while leaving the original RNA population
unperturbed, thereby reducing the potential for
the introduction of bias into the results. This
technology also ensures more efficient use of
sequencing resources by effectively depleting
ribosomal RNA reads when total RNA input is
used to prepare sequencing libraries. InDA-C is
the core technology used in the Ovation Human
Blood RNA-Seq System.
SPET (single-primer enrichment technology)
another innovative NuGEN technology,
maximizes the information yield from NGS
with a rapid and efficient sample-preparation
workflow. SPET is a target-enrichment tool
that allows for the simultaneous detection
of single-nucleotide polymorphisms (SNPs),
copy-numbers variants (CNVs) and insertions
or deletions. Until recently, CNV and sequence
analysis have required completely different
analytical platforms and sample preparation
to elucidate information for these three types
of genetic variation. SPET does so in a single
assay, conserving patient samples and making
more efficient use of sequencing resources.
SPET is the core technology used in the Ovation
Cancer Panel 2.0 Target Enrichment System.
SPET can also be used to identify gene-
fusion events and sequence variants in an RNA
sample. The SPET technology for targeted RNA
sequencing is flexible enough to target any
gene in any organism for gene-fusion detection
and gene-expression analysis. This will be an
important contribution to RNA-seq–based cancer
diagnostic and prognostic tests.
Real-world applications
Reproducible results from whole blood
PreAnalytiX and RUCDR Infinite Biologics part-
nered with NuGEN to develop and validate an
end-to-end workflow for the reproducible collec-
tion and processing of whole blood for RNA-seq
in clinical studies. The study team found highly
reproducible results across sites, operators
and equipment. “We have determined that the
PreAnalytiX-NuGEN integrated workflow ensures
reproducible, accurate and sensitive results in
RNA-seq of whole blood,” said Andrew Brooks,
COO of RUCDR Infinite Biologics, who led the
study. “Importantly, this integrated workflow
enables gene expression from total RNA, allow-
ing researchers to study both protein coding and
regulatory transcripts from human whole blood.”
Veracyte uses NuGEN’s RNA-amplification
and labeling technology in its microarray-based
Afirma Thyroid FNA Analysis assay for the strati-
fication of indeterminate thyroid tumors. The test
greatly reduces unnecessary surgical interven-
tion in patients and is reimbursed by Medicare
and numerous other health insurers.
Sample prep for clinical cancer
diagnostics
NuGEN is working with leading molecular-
diagnostics companies to develop and
commercialize genomic diagnostic and
prognostic tests. The enabling characteristics
of NuGEN’s sample-preparation technologies
translate well to clinical settings, in which
samples are often limited and whole blood and
FFPE samples are widely used. To facilitate
the translation of diagnostic research into
the clinic, NuGEN has established rigorous
quality standards, including ISO 13485:2003
certification and California State current good
manufacturing process (cGMP) licensure, making
it one of the first reagent companies to meet
these exacting qualifications.
NuGEN is a pioneer in developing innovative
sample-preparation solutions for targeted
genomic analysis. From the early days of
microarray technology to present-day NGS,
NuGEN has been a leader in the development
and manufacture of innovative technologies that
help bring the benefits of the genomic revolution
to all.
CONTACT DETAILS
Alan Dance, VP Marketing
NuGEN Technologies
San Carlos, CA, USA
Tel: +1-650-590-3671
Email: adance@nugen.com
Microscopic image of a circulating tumor cell.

DNAnexus, Inc.
www.dnanexus.com
Accelerating Precision Medicine
Utilizing cloud-based genome informatics to inform next-generation sequencing diagnosis and treatment.
I
n a dozen years, sequencing of the human
genome has been transformed from a
herculean task to one requiring as little as
a day and a thousand dollars. This dramatic
improvement in sequencing technology promises
important benefits to human health, but realizing
this potential in everyday practice requires over-
coming new challenges. DNAnexus, the global
leader in cloud-based genome informatics and
data management, offers a universal solution to
the informatics challenges posed by next-gener-
ation sequencing (NGS), providing the backbone
technology needed to apply NGS to the diagnosis
and treatment of disease (Box 1).
“Medical progress is driven by inquisitive and
impassioned clinicians, researchers and data
scientists determined to make a difference,” said
DNAnexus chief medical officer David Shaywitz.
“Our goal is to support and empower these
champions.” The DNAnexus Platform speeds
the delivery of clinical innovation to patients
with a turnkey computational and data manage-
ment solution that is efficient, customizable and
compliant with clinical regulatory demands, yet
flexible enough to integrate other NGS technolo-
gies into a customer specific pipeline. DNAnexus
serves a broad range of global partners, from
prenatal testing companies to the US Food and
Drug Administration (FDA).
NGS challenges
Delivering on the promise of NGS will require
overcoming critical challenges, including the
quantity of data involved, the need for compre-
hensive regulatory compliance, stringent controls
on patient data privacy and security, the need
for collaboration across institutional firewalls,
and integration with upstream and downstream
systems, including sequencing platforms. “Our
clinical customers need data management
to be HIPAA [Health Insurance Portability and
Accountability Act] compliant and secure at all
steps in the process. This becomes even more
important at scale, when petabytes of data are
involved,” explained Richard Daly, chief executive
officer at DNAnexus.
Extending global reach
DNAnexus has partnered with Natera, a leader
in noninvasive genetic testing, to support data
analysis,storage and sharing. Using the DNAnexus
Platform, Natera’s remote global partner laborato-
ries can upload sequencing data to a single secure,
CE-certified environment. This has allowed Natera
to rapidly expand into new markets by minimizing
IT friction points. According to Daly,“The DNAnexus
Platform serves as a compliant command center
supporting multiple testing sites and enabling pro-
viders such as Natera with the technical platform
to market and monetize their tests globally.”
In addition to geographic expansion, the
Platform is also designed to easily accommo-
date new product development and deploy-
ment. “DNAnexus has made it easy for us to
take advantage of cloud genomics by removing
the costs and technical headaches associated
with building a do-it-yourself alternative,” said
Jonathan Sheena, cofounder and chief tech-
nology officer of Natera.
Advancing cancer care
When Intermountain Precision Genomics, an in-
house laboratory for Intermountain Healthcare,
was searching for a bioinformatics solution, the
ability to share research data and rapidly scale
the effort across their 22 hospitals and medical
group was a key criterion. Intermountain and
DNAnexus worked together to develop a cloud-
based bioinformatics pipeline to translate raw
sequence data into interpretable variants. “We
selected DNAnexus because of the company’s
leading bioinformatics and cloud computing
expertise, combined with the best-in-class
security and compliance standards of the
Platform,” said Lincoln Nadauld, medical direc-
tor of Intermountain Precision Genomics. With
these data, Intermountain’s oncologists can
identify tumor-specific mutations and determine
the best treatment option for each patient.
“The underlying infrastructure that DNAnexus
provides allows us to focus on our core compe-
tencies of RD and patient care while revolution-
izing cancer treatment.”
Leading open-source NGS RD
As a leader in the field, DNAnexus was awarded
a contract to create precisionFDA, an open-
source platform for sharing of genomic-testing
information. As part of the White House’s
Precision Medicine Initiative, the FDA is tasked
with developing a streamlined approach to
evaluating diagnostics that rely on NGS technol-
ogy, and precisionFDA is a critical part of that
effort. DNAnexus anticipates that precisionFDA
will be used by test developers, standard-making
bodies, biopharmaceutical companies, health
care providers, academic medical centers and
patient advocacy groups.
For diagnostic developers, the precisionFDA
Platform offers a venue for comparing new tests
to approved ones and sharing results with col-
laborators and the FDA. As participants grow and
more NGS data become available, this grass-
roots effort is expected to generate reference
data sets and ultimately help to define industry
standards. “DNAnexus is proud to be creating
a community around open-source genomic-
analysis pipelines, reference data and analytical
processing resources,” said Daly. “The Platform
will enable the managing and sharing of genomic
data at an unprecedented level.”
BOX 1: THE DNANEXUS SOLUTION
Cloud-based › The DNAnexus approach
allows rapid upload to a secure cloud of
data files of all types, or of entire pipelines.
It facilitates the creation and validation of
custom workflows using either a command
line or a web interface. It offers an elastic
capacity to meet evolving needs, without
the need for capital investment in hardware
or ongoing infrastructure management.
Fast track to compliance › DNAnexus has
met HIPAA, Clinical Laboratory Improvement
Amendments (CLIA), good clinical practice
(GCP) and EU regulatory standards,
offering partners a quick, cost-efficient
path to compliant handling of NGS data at
all points in the workflow, from raw data
to final reporting, including incorporation
into electronic medical records.
Private and secure › The privacy and
security of patient data are paramount
for clinical applications. DNAnexus is
independently audited and certified as
compliant to ISO 27001, the internationally
recognized standard for information-security
management systems. Data is encrypted
at rest and in transit on DNAnexus.
Flexible › The DNAnexus application
programming interface integrates seamlessly
with other NGS upstream and downstream
system components, including lab information
management systems (LIMS) and reporting
software. The platform supports global access
to data, facilitating consistent workflows
and ensuring uniform analytical treatment
and reproducibility of results across sites.
CONTACT DETAILS
Tim O’Brien, Vice President, Sales
DNAnexus, Inc.
Mountain View, CA, USA
Email: sales@dnanexus.com

InvivoSciences Inc.
www.invivosciences.com
Predicting cardiotoxicity with
engineered 3D human cardiac tissue models
InvivoSciences harnesses human induced pluripotent stem cells to generate patient-
specific disease models for drug and diagnostics development.
C
ardiovascular safety liabilities
caused 52.3% of 44 marketed
drug withdrawals according to
data from 1980 to 2011, and cardio-
vascular disease remains the leading
cause of death globally, yet only 8.7%
of cardiovascular drugs successfully
pass clinical trials. These statistics
demonstrate the need to address a
patient’s specific genetic make-up and
phenotype by adopting a personalized
treatment methodology for cardiovas-
cular diseases.
Established in 2001 in St Louis,
Missouri, InvivoSciences Inc. (IVS) pro-
vides innovative solutions to address
the unmet technological needs in
drug discovery and development for
cardiovascular diseases and to predict
adverse cardiotoxicity effects at the
preclinical stage. Today operating in Madison,
Wisconsin,the founders work with scientific advis-
ers and collaborate with leading academic and
government institutions.
Drug discovery platform
IVS has become a leading developer of human
3D cell and tissue culture models by providing
a high-throughput, functional system for testing
cardio safety and efficacy to screen and identify
compounds or pathways that may alter cardiac
physiology and pathology. The high-content analy-
sis of human engineered tissues is instrumental
in drug discovery at their screening and lead opti-
mization stage. The IVS proprietary technology
allows the growth of engineered tissues in 3D to
mimic healthy and disease-naive human tissues,
which enables the gap to be bridged between cell-
based assays and studies using isolated organs,
tissues or animal models. The engineered tissue,
developed without a synthetic supporting layer,
allows physiological measurements (e.g., con-
traction) and analysis. IVS technology improves
clinical approval success rates by predicting
patients’ responses to drug candidates which
is achieved by using the tissue-based discovery
platform to predict patient-specific responses to
treatments in engineered human tissues derived
from patient-specific samples.
Abnormalities in muscle function are observed
in many inherited or acquired diseases, such
as muscular dystrophy, chronic obstructive pul-
monary disease, and congestive heart failure.
The Palpator is a high-throughput mechanical
tissue analyzer that measures the mechani-
cal properties of engineered tissues growing in
96- or 384-well plates and allows chemical library
screening. IVS has carried out proof-of-concept
studies to analyze the molecular mechanisms of
action of different compounds on the contractile
activities of different muscle cell types.
IVS provides services to develop heart failure
models driven by genetic mutations. Current
projects include phenotyping of patent-specific
engineered heart tissues (EHTs) for Duchenne
muscular dystrophy and congenital heart disease.
Precision medicine focus
Human induced pluripotent stem cell (iPSC)
technology is critical within precision medicine
because it generates a disease model in a dish.
The iPSC’s capacity to yield large numbers of
pluripotent cells able to differentiate into almost
any somatic cell type is attractive. However,
performing this feat industrially is daunting as
well-defined, uniform and reproducible patient
derived iPSCs are essential for cells to differenti-
ate into somatic cells and to develop tissues and
organs for faithful disease modeling. Automation
of iPSC culture can normalize and standardize
cell proliferation, enabling researchers to handle
large numbers of human cell lines. Moreover, the
personalized 3D human cardiac tissue models
empower researchers to conduct drug safety and
efficacy analysis using enriched study population
at preclinical stages.
IVS has developed an in vitro disease model
that recapitulates an individual patient’s cardio-
myopathy in 3D EHTs using patient-derived cells.
Automated cell culture and cardiomyocyte-differ-
entiation protocols demonstrate both improved
productivity and reproducibility for generating
patient-specific disease models for
drug and diagnostics development
(see figure).
Products and services
IVS’s products and services will reduce
the cost and use of animal studies. The
company’s assay platforms assess the
therapeutic efficacy of pharmaceutical
candidates by analyzing key physiologi-
cal functions of engineered tissues
in vivo. The Palpator is used for analyz-
ing the structural and mechanical integ-
rity of heart heart muscle equivalent.
The live-in-tissue analysis (LITA),a high-
content phenotypic analyzer, quantifies
treatment-induced changes in a tissue
construct’s physiological function and
the biomolecular activities that under-
lie those changes. IVS offers services
using the LITA for testing the efficacy and safety
of drug candidates. The LITA will soon be available
for in-house operations at customers’ sites and
is also available in other applications including
regenerative medicine, cancer, autoimmune dis-
orders and many rare diseases. IVS also provides
a device, ACTRO that automates cell and tissue
culture of iPSCs and can handle an increasing
number of patient-specific iPSC lines.
Future perspectives
US National Institutes of Health (NIH) Small
Business Innovation Research (SBIR) grants have
supported IVS’s drug discovery applications of its
innovative technologies, allowing the company to
build a strong foundation. The strategic collabora-
tions with key industry and academic partners
have helped IVS to create a unique product/assay
and service portfolio that provides solutions to
unmet needs in drug discovery and patient popu-
lations with debilitating cardiac diseases. IVS
has developed global commercial growth plans
by boosting its scaled-up and fully automated
manufacturing of human engineered tissues and
their personalized derivatives. IVS seeks potential
private funding partners to share the business
opportunity. IVS also wants to expand its strate-
gic partnerships with pharmaceutical and biotech
companies.
CONTACT DETAILS
Ayla Annac, CEO/President
InvivoSciences Inc.
Madison, WI, USA
Tel: +1-608-628-8035
Email: aannac@invivosciences.com
©2015InvivoSciencesInc.Allrightsreserved.

Biocartis NV
www.biocartis.com
Idylla: high-precision diagnostics
for high-precision medicine
Biocartis' molecular diagnostics make precision medicine simple.
P
ersonalized or precision medicine is a
fast-growing area that relies on targeted
medicines supported by fast, reliable,
sensitive and cost-effective in vitro diagnostics to
ensure that doctors are able to get the right drugs
to the right patients on the right timescale while
tracking their response to treatment. Belgian
company Biocartis NV, founded in 2007, aims
to provide next-generation diagnostic solutions
for improving clinical practice for the benefit of
patients, clinicians, payers and industry. Idylla is
Biocartis’ fully automated, real-time PCR-based
molecular diagnostics system, designed to
offer fast and easy access to clinical molecular
diagnostic information virtually anywhere and
any time. Idylla was commercially launched in
September 2014, and its track record so far has
convinced key opinion leaders in pathology, oncol-
ogy and infectious disease across the world of
its abilities.
Creating fast and accurate
molecular diagnostics
Molecular diagnostics is one of the fastest grow-
ing segments of the in vitro diagnostics market,
predicted to be worth around US$8billion world-
wide by 2018.
Clinical molecular testing currently involves a
series of complex, labor-intensive and relatively
costly steps, including preparation of clinical
samples; isolation of genetic material, such
as DNA; amplification, detection and quantifi-
cation of the genetic material; result delivery;
and—finally—interpretation by the pathologist.
Driven by the conviction that easier, more effec-
tive and near-patient use can help doctors select
a targeted therapy, Biocartis has developed the
CE-IVD–marked Idylla diagnostics system. It is
a rapid, highly sensitive, automated real-time
system that can be used on demand and at
point of need. All this in combination with its
capability to detect up to 30 molecular targets
in standard mode creates new possibilities. The
Idylla system consists of a console with a touch-
screen connected to an instrument that allows
Idylla cartridges to perform specific tests. The
cartridge includes all reagents and is designed to
handle a wide variety of different clinical sample
types, including tissue samples, blood, urine,
sputum, swabs and fine needle aspirates. With
an average hands-on time of just 2 minutes and
a turnaround time of 35–150 minutes, depend-
ing on the complexity of the test, Idylla can be
considered a fully automated PCR system.
Because of the current complexity of molecular
diagnostics (MDx), only a small subset of hos-
pitals are able to perform (complex) MDx tests
in-house. For most hospitals, the test volume is
too small to justify investment in the infrastruc-
ture, equipment and personnel needed to per-
form today’s MDx tests. With the Idylla platform,
this hurdle can be overcome: there is no need for
dedicated pre- and post-amplification rooms, and
handling is reduced to a level of such simplicity
that no specific skills in MDx are required, as no
complex steps or other equipment are involved.
In addition, with Idylla samples can be analyzed
one by one, whereas most current systems
require batches of samples for analysis. These
features could bring MDx within the reach of
smaller hospitals, so that they would no longer
have to send samples to centralized labs and
could thus save time in the diagnostics process,
which is a crucial advantage. For larger labs,
Idylla offers the ability to run samples between
batches, decreasing labor costs related to the
execution of tests, reducing user-induced vari-
ability between tests and offering a much faster
turnaround time. Idylla does this without sacri-
ficing quality. Idylla truly creates new opportuni-
ties for hospitals and laboratories.
Today Biocartis is rapidly expanding its test
menu to address key unmet clinical needs in
oncology and infectious diseases. Biocartis
recently made significant progress in the field
of liquid biopsies. In June 2015, Biocartis pre-
sented positive results of a research study,
conducted in collaboration with Bart Neyns from
the University Hospital Brussels, at the annual
meeting of the American Society for Clinical
Oncology, demonstrating that levels of BRAF-
mutant tumor DNA in the circulating blood of
metastatic melanoma patients were associated
with disease progression. This opens up the pos-
sibility of making patient monitoring easier and
less invasive.
Biocartis’ vision: growing into the future
Currently employing over 200 people, Biocartis
has plans for growth. Over the next few years,
the company aims to ramp up its release of MDx
tests to four or five a year, through a combina-
tion of in-house development and collaboration.
Biocartis’ direct sales team currently covers 16
European countries, and this reach will expand
worldwide as the company launches more prod-
ucts and Idylla gains regulatory approval in the
United States, Japan and China.
Hilde Windels (deputy CEO), Erik Vossenaar
(VP of business development) and Rudi Pauwels
(founder and CEO) are aware of the advantages of
good collaborations and strategic partnerships.
“Small and larger partners have contributed to
the success of Idylla, and the Idylla platform
has enabled partners to bring their innovation
to a new level. Biocartis is looking forward to
partnering with teams with the same drive and
mind-set, creating new opportunities in the fields
of MDx and high-precision medicine,” explained
Vossenaar.
CONTACT DETAILS
Erik Vossenaar, VP, Business Development
Biocartis NV
Mechelen, Belgium
Tel: +32 (0)15 632 600
Email: evossenaar@biocartis.com
The Biocartis team: Hilde Windels (left) and Erik Vossenaar (right).

Pacific Edge Ltd.
www.pacificedgedx.com
Groundbreaking, noninvasive
tests for bladder cancer
Pacific Edge has expanded the international market for two new molecular tests
that provide better detection and management of urothelial cancer.
T
wo groundbreaking,noninvasive diagnostic
tests for bladder cancer are the first of
four such new products to be successfully
launched by Pacific Edge, a company that spe-
cializes in the discovery and commercialization
of diagnostic technology for early detection and
monitoring of cancer.
Founded in New Zealand in 2001, Pacific Edge
identifies unique gene signatures and develops
them for its new class of cancer management
tools. It utilizes state-of-the-art molecular biology,
gene expression analysis and signature develop-
ment; proprietary biobanks for validation; clinical
data; and proprietary analytical software.
At the heart of the company’s products is its
urine sample–collection system. Only a small
volume of a patient’s urine is required, and is
safely protected for international transport,
enabling Pacific Edge to utilize its custom world-
wide laboratories.
Cxbladder Triage, which accurately identi-
fies patients with a low probability of bladder
cancer, and Cxbladder Detect, which identifies
bladder and other urinary tract cancers, are
both achieving rapid sales growth in the United
States, Australia and New Zealand; the tests are
undergoing evaluation by urologists in Southeast
Asia. Pacific Edge is positioning itself as a global
leader in cancer molecular diagnostics and a one-
stop shop for urologists.
Cost effective, accurate and precise
“There have been no new therapies for bladder
cancer for 30 years and no new commercially sig-
nificant diagnostic tests for bladder cancer in 15
years,” said David Darling, CEO of Pacific Edge.
“Our tests are noninvasive, cost effective
and accurate, and they provide urologists with
valuable new perspectives for clinical decision
making. This, combined with our urine sample
system, provides patients and clinicians with a
straightforward, noninvasive test that enhances
the patient experience and leads to better compli-
ance and patient outcomes.”
Cxbladder Triage combines the power of
genomic biomarkers with extra phenotypic and
clinical risk factors to accurately identify patients
with hematuria (blood in their urine) who have a
low probability of bladder cancer. It can reduce
the number of patients needing costly, invasive
work-ups for urothelial cancer, and is an essential
tool for urologists dealing with the many patients
who have hematuria but are unlikely to have uro-
thelial cancer.
Cxbladder Detect measures the expression
of five biomarker genes that represent a bladder
cancer signature. It is a quick, cost-effective
and accurate adjunct to cystoscopy and can
replace other urine-based tests or, in some
instances, remove the need for some of these
invasive tests.
Both products have been tested and vali-
dated in international, multicenter clinical stud-
ies1,2,4
. In the latest study, published in May
2015, BMC Medical Research Methodology
ranked four noninvasive bladder cancer diagnos-
tic tests on the basis of a study of 939 patients
across five data sets3
.
Researchers compared the tests on three
measures of accuracy: sensitivity, signal-to-
noise ratio and cross-validation error rate.
Overall, Cxbladder Detect outperformed the
other three tests (Table 1), including UroVysion
FISH, which is covered by all major insurance
companies in the United States.
Research on Cxbladder Triage was published in
BMC Urology in April 2015 and showed that 80 %
of patients with microhematuria who did not have
urothelial cancer were correctly triaged out and
could bypass a full work-up for urological cancer4
.
Two new products to launch
in 2015 and 2016
Pacific Edge will launch two more products in its
Cxbladder suite in 2015 and 2016: Cxbladder
Monitor and Cxbladder Predict.
Worldwide, bladder cancer is the sixth most
prevalent form of cancer (8 % for males and 2 %
for females), with a high recurrence rate. It car-
ries the highest medical cost per patient of all
cancers (US$240,000 from diagnosis to death).
“Pacific Edge’s products also address the
issue of a much larger patient population with
hematuria. Many more are worked up for blad-
der cancer than need be, at a high cost. The
Cxbladder technology provides solutions that
significantly lower those costs and focus treat-
ment and management on the people who need
it most,” Darling said.
In the United States, where Pacific Edge ana-
lyzes urine samples at its Clinical Laboratory
Improvement Amendments (CLIA)-certified
and College of American Pathologists (CAP)-
accredited laboratory in Pennsylvania, the market
potential is around 2 million tests each year.
Pacific Edge has agreements with the four larg-
est National Provider Networks (FedMed, ACPN,
Stratose and Multichoice) and is advancing
commercial relationships with private insurance
companies, integrated healthcare providers, the
Veterans Administration and the Centers for
Medicare and Medicaid Services.
User Programs, which allow urologists a trial
period for Cxbladder, have proven the most
effective component of Pacific Edge’s sales
strategy. Additional programs are being rolled
out internationally, including one with the United
States’ largest nonprofit health insurer and pro-
vider, Kaiser Permanente, and the first Southeast
Asian program with one of Singapore’s biggest
hospitals, Tan Tock Seng. The company also
plans to launch similar programs in Taiwan and
Thailand.
“Southeast Asia has considerable potential
for us, particularly because of the increasing
number of medical tourists. We use our CLIA-
certified laboratory in New Zealand and analyze
samples with a very quick turnaround time,”
Darling said.
The company has also launched a successful
ecommerce site for online ordering of Cxbladder
tests by New Zealand residents and healthcare
professionals. It will be replicated in other mar-
kets where possible.
References
1. Holyoake, A. et al. Clin. Cancer Res. 14, 742–749 (2008).
2. O’Sullivan, P. et al. J. Urol. 188, 741–747 (2012).
3. Breen, V. et al. BMC Med. Res. Methodol. 15, 45 (2015).
4. Kavalieris, L. et al. BMC Urol. 15, 23 (2015).
CONTACT DETAILS
David Darling, CEO
Pacific Edge Ltd.
Centre for Innovation
Dunedin, New Zealand
Tel: +64 (0)3 479 5800
Email: david.darling@pelnz.com
Table 1: Sensitivity and specificity of urinary
cancer diagnostic tests.
Product Sensitivity
(% (95 % CI))
Specificity
(% (95 % CI))
Cxbladder Detect 73.6 (65.1–81.7) 81.7 (78.7–84.4)
Cytology 46.0 (36.3–55.8) 95.3 (93.7–96.6)
NMP22 45.9 (35.9–56.3) 88.0 (85.5–90.2)
UroVysion FISH 47.7 (31.5–63.3) 87.7 (84.7–90.3)
CI, confidence interval. Source: Data from Breen, V. et al.
BMC Med. Res. Methodol. 15, 45 (2015)

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