A series of business profiles from leading biotech and pharmaceutical companies looking to develop
relationships with prospective partners. Featuring Cancer Partnering and Contract Services.
As originally published in the January 2010 edition of Nature Biotechnology
and the February 2010 edition of Nature Reviews Drug Discovery as an advertising feature.
A D VE R T I S E ME N T FE AT U RE
PUBLISHING TEAM Cancer Partnering Feature S2
Epeius Biotechnologies S7
Business Development Manager
Wellcome Trust S8
Business Profile Writers
Barbara Nasto Scil Proteins S10
Bravian Nordic A/S S13
Pergamum AB S14
Contract Services Feature S15
Note: Companies that appear in this
table of contents have paid for their
advertisement features and have final PharmaLegacy S22
approval of their content. If you would
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Dealmakers please contact: InvivoSciences LLC
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Discovery with a Human Touch
Business Development Manager
AD VE R T IS E ME N T FE ATU RE
There is no better way to figure out if a cancer drug is really working than to test it in patients
and there is no better way to improve that treatment than to feed information about the
patient’s response directly back to the manufacturer. That truth was what motivated Merck
to establish a relationship with the H. Lee Moffitt Cancer Center & Research Institute (MCC) in
Tampa, Florida three years ago. The multi-site project involves the analysis of tumor tissues
and clinical data from thousands of patients.
The installation in 2008 of a high-level IT framework called the Biomarker Information
Pipeline has facilitated progress. Upon enrolling in the MCC’s Total Cancer Care program,
patients sign a consent form and a random number is generated for each sample, thus de-
identifying them. Data is automatically uploaded into a data warehouse without any human
intervention. Standard operating procedures are in place to ensure that tissue samples are
collected and processed consistently. At the end of each day the patient data are sent by MCC
to Merck for analysis. The results are then transmitted back to the center. “It’s all about trans-
lating what we learn on the molecular level into what we know about patients,” says Merck’s
Dr. Mervyn Turner. “We get the opportunity to profile different types of tumors and to see if
our ideas about pathway biology are reflected in real life.”
Merv Turner, Merck & Co., Inc
Getting the right drug to the right patient is just part of the equation. With the win-
dows of opportunity for treatment too few and far between, time is of the essence. In 2005,
AstraZeneca forged a strategic alliance with the M.D. Anderson Cancer Center in Houston,
Texas which included a master agreement for clinical and translational/preclinical research
specifying terms for standard items. The idea was to ensure that research projects and clinical
trials would not be held up by lengthy negotiations.
In August 2009 the two organizations reported that their efforts to collapse timetables—a
project aptly dubbed, Zero Delay—had succeeded. Just two days after the FDA approved a
first-in-human cancer trial, the patient number one was enrolled. According to the report’s
C A N C E R PA R T N E R I N G F E AT U R E
lead author, Dr. Robert C. Bast, Vice President for Translational Research at M.D. Anderson, the
time between having a complete written protocol and enrollment is typically 135 days. With
Zero Delay in place, that time was cut to 46 days with FDA clearance of the IND on day 44.
What changed? Most of the tasks were done in parallel in stead of sequentially. What’s more,
administrative tasks such as budget and contract negotiations, site visits, preparation, training
and mandatory reviews all were conducted prior to the FDA’s final ruling.
“Zero Delay demonstrates what can be accomplished in an atmosphere of trust and cool-
aboration that we’ve cultivated through out strategic alliance with AstraZeneca,” noted Bast in
a recent press release. “The next challenge,” he says, “will be to do this consistently in order to
develop truly innovative therapies that will someday offer new benefits to cancer patients.”
Kathleen Sereda Glaub, Plexxicon
mutation in oncogenes such as K-RAS or B-RAF The company has developed a selective BRAF
helps to predict how patients suffering from meta- inhibitor for mutation-positive melanoma patients
static colorectal cancer respond to certain EGFR and other mutation-positive cancers, PLX4032.
inhibitors. Monoclonal antibody treatments often “When we first read about the oncogenic mutation
cost about $50,000 but work only in those indi- in BRAF that drives about 50% to 60% of all mela-
viduals without mutations in the corresponding nomas and some 8% of all solid tumors we were
oncogenes. intrigued, especially since this mutation only occurs
“Qiagen is currently active in several col- in the tumor cells,” Glaub recalls. “Given our plat-
laborations for the development of novel bio- form to make particularly selective kinase inhibi-
markers and companion diagnostics and has tors, we reasoned that a highly selective inhibitor
relationships with seven of the leading players should provide for a very wide therapeutic window.”
in oncology,” reveals Marie-Claud Marchand, Researchers at Plexxikon have since discovered that
Senior Global Marketing Director for Pharma at while it is possible to modulate biomarkers with
Qiagen. Marchand believes that the links between 50% inhibition of the target, over 90% inhibition
markers and pathways will be very important to of the target is necessary to see tumor shrinkage
support therapy combination in cancer disease in patients. “Without a highly selective inhibitor, it
management. may not be possible to witness such efficacy due to
The sentiment is shared by Kathy Glaub, off target toxicities encountered before hitting the
Marie-Claude Marchand, Qiagen
President of Berkeley, California-based Plexxikon. 90% inhibition hurdle,” Glaub says.
A DV ER T I SEMENT FEAT URE
In 2005, Plexxikon entered into a partnership Take No Prisoners
with Roche Molecular Systems to create a com- One of the most frustrating aspects of treating
panion diagnostic to identify best responders for cancer is that patients often relapse. To prevent
PLX4032. A year later the company signed an cancer from finding escape routes unknown to
agreement with Roche Pharma to develop and current therapies, Merrimack Pharmaceuticals,
commercialize the drug. “Roche has initiated headquartered in Cambridge, Massachusetts, used
a Phase II pivotal trial in September 2009 and a its considerable expertise in network biology to
Phase III controlled study in December on a high- find those hidden trails and block them. Using this
ly accelerated timetable,” notes Glaub. “We have technique, Merrimack Pharmaceuticals has devel-
also transitioned PLX4032 to a life cycle team that oped MM-121, a fully human monoclonal antibody
integrates Roche and Genentech individuals with designed to block signaling of the ErbB3 receptor,
the best experience and expertise to move the a common mechanism of resistance to current
program to the next level.” therapies that cancer cells use to continue growing.
Another way to pinpoint the target is through MM-121 will be used in conjunction with other
diagnostic imaging. German pharmaceutical therapies to prevent rapid resistance to emerging
giant Bayer Schering Pharma AG is developing a therapies.
range of radioactive traces for binding to certain In October 2009, Merrimack signed its first
types of tumors. “We see a closer and closer link partnership — a licensing agreement with Paris,
Michael Yeomans, Bayer between the diagnostic, which can help you really France-based sanofi-aventis. “It is wonderful to
focus in on tumor type, and the treatment,” notes find a partner who believes in what we are doing
Dr. Michael Yeomans, Head of Global Business and has the confidence to let our approach lead
Development & Licensing for Bayer. “We are very MM-121 through Phase II proof of concept devel-
interested in the personalized approach to can- opment,” declares Ulrik Nielsen, Merrimack’s Chief
cer treatment,” he continues. “There has been a Scientific Officer and a co-founder. Under the
great explosion of knowledge in the whole oncol- terms of the agreement, sanofi-aventis is respon-
ogy field and the underlying causes and mecha- sible for all development costs as well as Phase III
nisms of the disease. We are learning more each clinical trials. Merrimack retains the right to co-
C A N C E R PA R T N E R I N G F E AT U R E
day about which drugs can help to treat specific promote the therapy in the US.
tumor types.” “We see network biology as a way to continue
the science beyond the event of creating the drug,”
Bayer Schering Pharma’s mission is to provide new treatment options for diseases with high
unmet medical need. In no area is this more apparent than in cancer where deaths are pro-
jected to rise to an estimated 12 million worldwide per annum by 2030. The big killers — lung
(1.3 million deaths/annum), stomach (803,000), colorectal (639,000), liver (610,000) and breast
Bjarte Reve, Oslo Cancer Cluster (519,000) — cost healthcare systems everywhere billions of dollars and continue to defy the
efforts of thousands of scientists and physicians.
In an attempt to accelerate the transition from basic research to promising treatment
options, Bayer has started a program called “From targets to novel drugs”. The program sup-
ports collaborative research projects in several areas with oncology heading the list. “We are
taking the initiative to reach out to the academic community and small companies who have
interesting or novel targets in oncology. We are asking them to share their ideas with us and
providing some level of financial support,” explains Bayer’s Dr. Michael Yeomans. “We got quite
a good response.”
The Oslo Cancer Cluster is hoping to capture the imagination of would-be oncologists and
research specialists before they ever enter the halls of advanced learning. The nonprofit has
signed an agreement with the City Council of Oslo and the Norwegian Radium Hospital to build
the world’s first innovation park to integrate a high school. Due for completion in 2012, the Oslo
Cancer Cluster Innovation Park will afford students the opportunity to receive guest lectures
from researchers and do internships at the Norwegian Radium Hospital or at one of the 40
member companies within the Cluster.
According to Kaare Norum who is chairman of the board for the Oslo Cancer Cluster
Innovation Park, “This endeavor will ensure and strengthen the recruitment to life science and
research and at the same time improve the quality of the education within math, science, phys-
ics, and health.”
A DV ER T I SEMENT FEAT URE
(Herceptin), coupled with one of ImmunoGen’s kinases. “We put it all together like the Army Corps
proprietary cell-killing agents that is attached to of engineers in a beautiful, elegant seek-and-destroy
the antibody using a specially engineered linker. vehicle which does just what it was designed to do,”
T-DM1 is in advanced clinical testing for the treat- says Hall.
ment of HER2-positive metastatic breast cancer Hoping for US regulatory approval shortly,
and has shown encouraging activity in patients Epeius is poised to explore its first partnership
whose breast cancer progressed on Herceptin and beyond the growing group of medical oncologists
other agents. who are recommending Rexin-G as “best care” for
“Genentech brought to the collaboration not patients. Hall emphasizes, “We are striving to gain
only the Herceptin antibody, but also extensive the first approvals for Rexin-G with the realiza-
clinical experience in the development of HER2- tion that many patients with otherwise intractable
targeting antibody-based therapeutics,” notes Peter cancers may benefit once tumor-targeted Rexin-G
Williams, Vice President of business development becomes available in the medical oncologist’s
for ImmunoGen. “In turn, we contributed not only arsenal.”
our cell-killing agent and linker technology, but
also assisted with aspects necessary for the timely Forward March
advancement of a conjugate compound, such as the Beyond the 861 cancer therapies currently on
development of a commercial-scale manufacturing the runway, hundreds, if not thousands more are
Campbell Wilson, AstraZeneca process.” on the way. Infinity Pharmaceuticals, located in
Cambridge, Massachusetts, has developed a novel
Stealth Bomb inhibitor of the Hedgehog signaling pathway called
All who fight cancer are united in their desire to IPI-926. Derived from the natural product cyclo-
deal the final blow. But annihilating tumors with- pamine which binds to and inhibits a key regula-
out killing the humans who have them has proven tor of this pathway, IPI-926 is being evaluated in
to be an endlessly elusive goal. One company in San a Phase I clinical trial in patients with advanced
Marino, California called Epeius Biotechnologies solid tumors. A year ago, Infinity created an alli-
believes it has a way to get at the heart of the dis- ance with Purdue Pharmaceutical Products L.P.
C A N C E R PA R T N E R I N G F E AT U R E
ease using the precision technology of a stealth and Mundipharma International Corporation to
bomber in the form of a broad-spectrum, tumor- develop and commercialize the compound. The
targeted, bio-compatible, systemically-injectable connection is paying off.
genetic medicine called Rexin-G. “Part of the courting process in business devel-
“Physicians and others need to learn that genet- opment is figuring out with whom you are best
ic medicine is not the enemy, it is the future,” pro- matched,” explains Adelene Perkins, President
claims Dr. Frederick Hall who co-founded Epeius and Chief Business Officer for Infiinity. “I spent
and today serves as its CEO and Chief Scientific a lot of my career putting partnerships like this
Officer. Rexin-G, which is commercially avail- in place. We always work hard to get it right,
able in the Philippines and has received Fast Track yet despite our best efforts, they often are tough
Designation from the FDA, has been administered to live out. I can say that with this partnership,
Adelene Perkins, Infinity in escalating doses as a stand alone therapy to a living the relationship out is better than the way
number of patients with late stage disease and been we structured it on paper,” she adds. “The objec-
shown effective in chemotherapy-resistant sarco- tive of the relationship—to develop a pipeline of
mas, prostatic cancer, malignant melanoma, and robust oncology products—defines the way we
pancreatic cancer. need to operate.”
Embodied within Rexin-G is a pathotropic or The war against cancer wages on. What once
disease-seeking targeting mechanism based on looked like miracle drugs are now considered
the von Willebrand factor. This complex protein blunt instruments, but we are still no where near
attaches to and guides the platelet to the site of vas- a cure for the most lethal forms of the disease.
cular injuries to initiate the clotting process while AstraZeneca’s Wilson is optimistic. “The search
laying down several powerful growth factors at the for an agent that is efficacious against many tumor
precise place of injury. Epeius was able to re-estab- types in a wide range of patients will continue both
lish this wound-seeking capacity onto the envelope in academia and in the pharmaceutical/biotech
of another structurally durable, widely-circulating sector. Approaches that harness the host’s own
smaller medicinal unit. immune system offer the most promise,” he says.
Equally critical to the efficacy of Rexin-G is its “However, it is much more likely that progress will
therapeutic payload which destroys cancer cells be made in small increments by developing nar-
with broad spectrum bioactivity. Creating this rower spectrum agents in conjunction with a diag-
required an appreciation of the common final path- nostic, thereby increasing the chances of efficacy in
ways of cellular growth control which are governed a given patient group and by the use of such agents
by the cyclin-dependent proline-directed protein in the right combination.”
AD VE R TI SE M E N T FE AT U RE
Epeius Biotechnologies, San Marino, CA, USA
w w w.epeiusbiotech.com
The Way to Seek and Destroy
It is the hope of every oncologist to eradicate life-threat-
Epeius Biotechnologies was born
ening tumors safely, without threatening the lives of their
out of inspiration, compassion,
patients. At Epeius Biotechnologies, we have found a way
and invention. The company has to do just that. We use a sophisticated precision-targeted
created the first broad-spectrum, delivery system combined with stealth lipid envelope-
tumor-targeted, bio-compatible, cloaked nanoparticles that are virtually invisible to the
systemically-injectable genetic patient’s immune system and are neither inflammation-
medicine for cancer. Called provoking nor immediately inactivated by the immune
Rexin-G, the anti-cancer agent is system. As a result, we have been able to successfully
precise, selective, and extremely develop a cancer treatment named Rexin-G that allows for
effective. Thus far, Rexin-G is administration through repeated intravenous infusions—
commercially available in the all without untoward side effects.
Philippines. In Japan, where
Rexin-G was administered to 35 Precise, effective and safe—by design
patients, 75% experienced long Embodied within Rexin-G is a pathotropic or disease- Hundreds of millions of Rexin-G nanoparticles are injected
into the patient intravenously (a) where they circulate in
term benefit. In the U.S. Rexin-G has seeking targeting mechanism based on the surveillant the bloodstream seeking out tumors and accumulating
received Orphan Drug designation hematological protein, von Willebrand factor. This com- selectively (c) in metastatic lesions (inset). Armed with the
for three clinical indications, as plex protein attaches to and guides the platelet to the site human cyclin-G1 gene knockout construct as its molecular
well as FDA Fast Track status. of vascular injuries to initiate the clotting process while payload, the nanoparticles (enlarged in b) enter into a
laying down several powerful growth factors at the precise proliferative target cell where the therapeutic gene triggers
Recent studies have shown clinical the production of numerous copies of the cytocidal gene
remissions in chemotherapy- place of injury. Epeius was able to re-establish this wound- product, thereby disrupting cell cycle progression, induc-
resistant sarcomas, prostatic seeking capacity onto the envelope of another structurally ing apoptosis in tumor cells and attendant vasculature, and
cancer, malignant melanoma, and durable, widely-circulating, and markedly smaller medici- causing tumor regression (d to f).
pancreatic cancer using Rexin-G as nal unit.
stand-alone therapy. Equally critical to the efficacy of Rexin-G is its thera- On a fast track
peutic payload which destroys cancer cells with broad Historically, this represents a significant advancement in
In addition to its strong IP portfolio, spectrum bioactivity. Creating this property required an genetic medicine, as well as clinical oncology—providing
Epeius has developed a network appreciation of the common final pathways of cellular the world’s first tumor-targeted gene-based medicine to
of eminent medical oncologists growth control which are governed by the cyclin-depend- be fully validated in the clinic. After gaining regulatory
who are currently recommending ent proline-directed protein kinases. When cyclin G1 is approval in the Philippines, Rexin-G was granted Orphan
Rexin-G as “best care” for patients expressed, the cell cycle advances. Conversely, when cyclin Drug Status for pancreas cancer, osteosarcoma and soft tis-
with refractory metastatic cancer. G1 is blocked, proliferative cells, including cancerous ones, sue sarcoma, as well as Fast Track Designation for pancreas
PA R T N E R I N G P R O F I L E
The company received approval die. Indeed, the name, Rexin-G, reflects its engineering cancer by the U. S. Food and Drug Administration.
from the Philippines in December roots: Retroviral expression vector bearing an inhibitory At this point, the scientific, biotechnological,
2007 for use against all solid construct of the gene-cyclin G. and biopharmaceutical heavy lifting have all been
tumors. To support the expanding accomplished, as has the landmark clinical valida-
clinical indications for Rexin-G, End-stage patients in clinical remission tion. Currently, we are on the very cusp of regulatory
Epeius Biotechnologies recently To us, no one matters more than the individual cancer approval for Rexin-G in the U.S. and are currently writ-
completed the construction of a patient. After years of indefatigable effort in clinical devel- ing advanced protocols for Phase III pivotal trials. We
state-of-the-art GMP compliant opment, treating one very sick person at a time, we have are striving to gain the first approvals for Rexin-G with
facility for the large scale finally achieved both progression-free survival and overall the realization that many patients with otherwise intrac-
production of targeted genetic survival benefits in significant numbers. The results of our table cancers may benefit, once tumor-targeted Rexin-G
medicines. latest U.S. clinical trials confirm those of our pioneering becomes available in the medical oncologist’s arsenal.
studies conducted in the Philippines, where Rexin-G has Meanwhile we are reaching out to biopharmaceutical
recently been approved for the treatment of all solid can- partners and cancer centers that are in a position to play
cers. Upon administering Rexin-G at optimal dosages to a constructive role in this inspired medical mission. It is
Dr. Frederick L. Hall
patients with Stage IV pancreatic cancer, more than 28% no longer impossible to imagine that metastatic cancer
CEO, CSO, and co-founder
of these otherwise poor-prognosis patients are surviving can be overcome by innovations in medical delivery and
475 Huntington Drive beyond one year. Similar gains in survival benefits are seen that more lives can be saved—once the essential concepts
San Marino CA 91108 in both osteosarcoma and soft tissue sarcoma. Three recent of pathotropic targeting are fully appreciated and the
Phone: + 1 (626) 441-6695 cases involving patients with late stage osteosarcoma, surveillant properties of tumor-targeted nanoparticles
Fax: + 1 (626) 441-6692 intractable prostate cancer, and pancreas cancer, further are deployed in modern medical practice. The advent of
Email: email@example.com demonstrate that Rexin-G, used as a stand alone treatment, pathotropic medicine in the treatment of metastatic cancer
www.epeiusbiotech.com can beat back the disease into clinical remission. represents a quantum leap indeed.
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w w w.wellcome.ac.uk/techtransfer/biopharma
Seeding Drug Discovery: Funding and
The Wellcome Trust’s £91 million Seeding Drug Discov- Two of the earliest projects funded under the ini-
The Wellcome Trust’s £91 ery initiative was launched in 2006, with the objective tiative, aimed at identifying inhibitors of BRAF and
million Seeding Drug of developing drug-like small molecules that will be the 11β-hydroxysteroid dehydrogenase (11β-HSD1), have
springboard for further research and development by the now come to fruition and produced preclinical drug can-
Discovery initiative was
biotechnology and pharmaceutical industry in areas of didates with supportive data and profiles that make them
launched in 2006 to develop unmet medical need. attractive for development into effective new therapies.
drug-like small molecules that The initiative aims to facilitate interdisciplinary We are now seeking commercial partners to take these
research groups within academic, biotechnology and candidates forward through clinical trials and towards
will be the springboard for pharmaceutical companies to engage in innovative, market.
further research and early-stage drug discovery projects that build on novel Strong patent portfolios exist for each programme with
development by the perspectives from the study of disease mechanisms or the all key commercial territories pursued, for which the Well-
activity of compounds. Programmes have been supported come Trust has the clear right to agree and negotiate with
biotechnology and that are complementary to existing R&D programmes in potential partners for all programmes that are undertaken
pharmaceutical industry. industry and are driven to a target product profile for within academic or research institutes.
which pharmaceutical companies or other organisations We are flexible on the business model for partner-
Two projects funded under see the technology as attractive because of a reduced level ing with our licensees, and would be pleased to consider
the initiative, aimed at of early-stage risk. either a straight licensing deal or those with a more col-
identifying inhibitors of BRAF Seeding Drug Discovery
and 11β-hydroxysteroid • The initiative has considered 280 preliminary For more information about Seeding Drug Discovery
applications to date, of which half have focused on at the Wellcome Trust see:
antimicrobial and oncology indications. www.wellcome.ac.uk/techtransfer/biopharma
have now come to fruition and • It has already completed six rounds of funding,
produced preclinical drug committing £67.9 million.
• It has established a broad portfolio, supporting
candidates with supportive 21 active research programmes across all main
data and profiles that make therapeutic areas, in the UK, Europe and the USA.
them attractive for • Two-thirds of active programmes are within
academic or research institutes, for which the Trust
development into effective negotiates the exploitation of assets.
new therapies. • Calls for proposals are made every six months, with
the final deadline for proposals in May 2010.
PA R T N E R I N G P R O F I L E
The Wellcome Trust is now
seeking commercial partners
to take these candidates
forward through clinical trials
and towards market.
Structure of 11β-HSD1 co-crystallised with an Edinburgh
For more information see: 11β-HSD1 inhibitor.
Seeding Drug Discovery is an initiative focused on the Oral therapeutic efficacy of selected candidate
early development of small molecule therapeutics. compounds in BRAF-driven melanoma xenograft model
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11β-HSD1 inhibitors BRAF inhibitors
We can offer opportunities for licences to a patent estate We are seeking a partner to license the worldwide rights
that include a worldwide exclusive licence on novel to develop novel BRAF inhibitors developed by a team
classes of clinical candidate 11β-HSD1 inhibitors and of researchers – funded jointly by Cancer Research
non-exclusive licenses to the therapeutic use of inhibi- UK (CR-UK) and the Trust – at the Institute of Cancer
tors of 11β-HSD1. Research (ICR) in London.
Chronically elevated glucocorticoid levels cause obes- The role of BRAF in cancer was first highlighted by
ity, diabetes, heart disease, mood disorders and memory scientists at the Wellcome Trust Sanger Institute in Cam-
impairments. 11β-hydroxysteroid dehydrogenase type 1 bridge and the ICR, who published a paper in Nature in The University of Edinburgh campus at
(11β-HSD1) catalyses intracellular regeneration of active 2002 showing that a mutation in the BRAF gene occurs Little France, where world-class research
glucocorticoids (cortisol and corticosterone) from inert in up to 70 per cent of malignant melanomas and around facilities are co-located with clinical
11-keto forms in liver, adipose tissue and brain, amplify- 7 per cent of all human cancers (including 30 per cent of research in a major teaching hospital and
ing local action. Seminal observations that 11β-HSD1 thyroid cancers, 30 per cent of ovarian cancers and 15 with commercialisation activities in the
activity is increased in key tissues in disease, and that per cent of colorectal cancers). Edinburgh BioQuarter.
reducing intracellular cortisol levels by inhibiting 11β- BRAF is a key part of the MAPK signalling pathway
HSD1 activity is beneficial in preclinical and human that stimulates cell proliferation, and has been shown to
studies, has validated this target in various diseases, drive tumour growth.
including type 2 diabetes and obesity, age-related cog- The core BRAF inhibitor drug discovery research
nitive decline and myocardial infarction. teams at the ICR are based in the laboratories of Profes-
The identification and elucidation of the physiologi- sors Richard Marais, an author of the landmark 2002
cal and pathophysiological roles of 11β-hydroxysteroid Sanger Institute paper, and Caroline Springer at the
dehydrogenases have been led by the team of Professors CR-UK Centre for Cancer Therapeutics – a renowned
Jonathan Seckl and Brian Walker at the University of onsite drug discovery unit that has developed many
Edinburgh, and supported by the Wellcome Trust for novel anticancer drugs.
over 15 years. The Trust has been responsible for main- The research teams identified four novel series of
taining and prosecuting to grant a patent estate on the compounds from a high-throughput and structure-
therapeutic use of inhibitors of 11β-HSD1. To ensure based design campaign, generating a panel of over
that the field of use in the search for novel inhibitors 450 compounds that can inhibit BRAF. Three of these
is not restricted, we continue to provide freedom to series were subjected to an extensive hit-to-lead and
operate with non-exclusive licences to those active in lead optimisation programme. As a result, the most
the field. potent compounds display excellent activity against
With Wellcome Trust support, the Edinburgh group BRAF. Investigation of the ADME properties of these
established an in-house drug discovery capability in compounds indicated they are cell-permeable, with
2003, headed by Dr Scott Webster. It operates within a good CYP450, hERG and microsomal stability profiles.
large University research group with world-leading tools These orally bio-available preclinical candidates have
PA R T N E R I N G P R O F I L E
and expertise in all relevant biology, and in collabora- differing selectivity profiles, and inhibit tumour growth
tion with a major global medicinal chemistry company, in BRAF-driven melanoma and colorectal carcinoma
to discover and optimise several series of 11β-HSD1 xenograft models.
inhibitors. A recent £5 million Seeding Drug Discov- All three candidates are at the same stage of devel-
ery award enabled them to develop and patent a series opment.
of optimised preclinical candidates with favourable in Our licensee can receive rights to all of the com-
vivo pharmacokinetic and pharmacodynamic character- pounds developed in the programme and can choose to
istics and efficacy in preclinical models. Of these series, develop any or all of these three preclinical candidates,
the group has selected a clinical candidate to advance depending on their specific requirements and the target
into phase I clinical trials, and is now conducting for- product profile they are seeking.
mal enabling toxicological studies prior to regulatory Our future partner will also, if they wish, have access
submission. Bespoke pharmacodynamics and efficacy to expertise at the ICR, which, in partnership with the
biomarkers developed in Edinburgh are available to sup- Royal Marsden NHS Foundation Trust, forms the larg- CONTACT DETAILS:
port early clinical development. est comprehensive cancer centre in Europe and one of For information on BRAF inhibitors:
We are seeking a commercial partner to license this the largest in the world; several drugs discovered or Dr Morag Foreman
orally bio-available candidate for further development developed there have successfully entered the clinic
and full efficacy clinical trials. The preferred licensing and reached the market. The ICR and Marsden teams
Tel: +44 (0)20 7611 8753
partner or partners may also access the expertise, knowl- are well placed to provide support for this project going
edge and tools of this world-leading research group in forward, as required. In particular, the teams are well For information on 11β-HSD1 inhibitors:
Edinburgh in order to gain unique advantage in this placed to write the first clinical trial protocol and con- Dr Richard Davis
very competitive field. duct the first trial. Email: firstname.lastname@example.org
Tel: +44 (0)20 7611 8287
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w w w.scilproteins.com
Scil’s scaffold skills
Over the past decade, antibody-based therapeutics have of immunogenicity, and greater preclinical predictability.
Scil Proteins is a privately held made a huge impact on how patients are treated. Indeed, “Affilin® molecules are small proteins of about 78
biotech company active in the some of the most important, clinically effective and best- amino acids and 8.4 kilodaltons in size, and because they
selling cancer drugs are based on monoclonal antibod- are derived from a human serum protein, they are not
area of protein therapeutics.
ies. However, despite the well-documented advantages immunogenic. In addition, ubiquitin possesses an immu-
The company’s technological of high specificity, affinity, and acceptable safety profiles, nosuppressive domain that has developed in nature,
basis is the proprietary Affilin® antibodies are not without their limitations which has which reduces even further any immunogenic risk of our
inspired the development of alternative approaches. engineered Affilin® derivatives,” he added.
protein therapeutics platform.
“Antibodies can trigger immune responses, have poor Immunogenicity is always an issue when using scaf-
From highly complex libraries, tissue penetration, normally require delivery by injection, folds and protein engineering in drug discovery.
Affilin® therapeutics are are often very expensive to make, and have poor ther- Another important differentiator of Affilin®, accord-
mal stability,” notes Henning Afflerbach, Chief Business ing to Afflerbach, is that the ubiquitin molecule is highly
screened and selected for Officer at Scil Proteins. conserved throughout the animal kingdom. “This means
binding disease-related Moreover, intellectual property covering the area is that the ubiquitin of the fruit fly, mouse, and monkey is
targets with high affinity and very complex and reduces the freedom of developers identical to humans. Consequently, Affilin® molecules
to operate. can be tested in all animal models without the need of
selectivity. A specific strength Consequently, a number of new approaches that surrogates,” he added.
of Scil Proteins is to combine embrace the advantages of antibody therapeutics while Scil Proteins has created libraries of Affilin® molecules
attempting to minimize the disadvantages are now by engineering the surface of the ubiquitin protein to cre-
elevated capabilities and
emerging and are beginning to make a serious contribu- ate new binding sites that can be easily produced in bacte-
cutting-edge techniques in tion to the development of new cancer treatments. These ria. These changes do not alter the overall protein struc-
drug discovery with strong approaches are mostly based around antibody fragments ture nor its stability. Using phage and ribosome display
or protein scaffolds and have been the focus of some high technologies that it has either acquired or in-licensed,
expertise in the contract profile and high value acquisitions and licensing deals. Scil is able to select Affilin® molecules that bind to specific
biomanufacturing field. This “What all these protein scaffolds have in common pre-defined targets.
includes full process is that they are small, relatively easy and less expensive “We start with the exposure of an antigen to our
to manufacture, are very stable, can penetrate deep into library. We use the TAT phage display and ribosome dis-
development and GMP tissue, and can have high affinity and specificity against play technologies, which are fast, robust and effective, to
production of recombinant certain disease-related targets,” notes Afflerbach. screen those Affilin® candidates that bind to the targets.
As a relatively late entry into the post-antibody space, It takes about ten weeks to go from original hit identifica-
proteins in microbial systems.
Scil Proteins has developed its own drug discovery plat- tion through protein characterization to determining the
form — Affilin® molecules. Affilin® is based on the human affinity of the Affilin® hits,” added Afflerbach.
PA R T N E R I N G P R O F I L E
serum protein ubiquitin and will enable drug companies Scil accessed the ribosome display technology
to develop highly effective treatments. While it has many from Cambridge Antibody Technology, now part of
of the attributes common to other post-antibody plat- AstraZeneca’s MedImmune unit, in 2006 and acquired
forms, the Affilin® platform has some qualities that make the TAT technology from the University of Berlin in
it an attractive drug discovery option, such as reduced risk September 2009.
Comparison of Affilin® molecules with conventional small molecule drugs Competitive features of Affilin® molecules
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Schematic representation of Affilin® display technologies, A) ribosome display Affilin® toxin fusions are enriched at tumor cells. In healthy cells the fusion is
and B) TAT phage display rapidly destroyed by the proteasome. In tumor cells the toxin is released
through specific cleavage, leading to cell death
From the billions of different Affilin® molecules ini- published for ubiquitin toxin fusions,” he added.
tially screened, Scil will subject 100 or so for detailed Interestingly, if some leakage of the Affilin®–toxin
characterization. These selected molecules will already conjugate into healthy cells occurs, there is no cleavage
display dissociation constants in the low nanomolar of the complex, owing to the absence of the tumor-spe-
range with high target specificity. cific protease, but instead the ubiquitin scaffold mediates
“We have so far generated two very complex librar- transfer to the proteasome complex, where the toxin gets
ies around a monomeric and dimeric format. The mon- degraded and inactivated.
omers are very small, very stable, and very effective, but “What we are currently doing is choosing targets that
sometimes we have to deal with issues relating to spe- are clinically validated where we have seen convincing
cificity which we can improve if we add another bind- clinical data and there is an opportunity for us to go into
ing module to a monomer to create an Affilin® dimer. different indications and create a best-in-class oppor-
Ubiquitin is easily manipulated, so it is something that tunity,” he added. This does mean, however, that Scil is
we can do to improve binding, half-life properties, or to ignoring cancer targets, such as CD20 or VEGF, which
support multiple targeting,” he added. are currently well-served by other approaches.
So far, Scil has achieved picomolar affinities, com- Affilin®-based molecules can also be used in diagnos-
pleted pharmacokinetic and toxicity studies, and shown tics and analytics, and in chromatography applications.
PA R T N E R I N G P R O F I L E
that it can create Affilin®-based molecules with high The specific coupling of Affilin® molecules to matrices or
specificity against cancer cells. surfaces and their robust behavior underpins their poten-
Scil envisages Affilins being useful either on their tial use in protein chip technologies. Also, the fast clearance
own, as monomers or dimers, against cancer or inflam- and straightforward coupling of labels to Affilin® makes
mation targets —where they might block key receptors, them attractive as tools for in vivo diagnostic imaging.
cytokines or recruit other effector molecules — or as To date, Scil Proteins has entered into agreements
conjugates — where they essentially carry a therapeutic with academic partners to provide its technology for
payload to a specific disease site. the development of Affilin®-based products. Scil is now
The conjugates Scil is looking at involve pro-apop- looking to find partners for Affilin-based therapeutics
totic cytokines, which bring cell death to the binding that the company has already generated against clinically
site, or radio-labeled molecules or cell toxins. validated targets, or to partner with companies that have
Indeed, Scil is going to take advantage of a unique proprietary disease-related targets that they would like to CONTACT DETAILS:
property associated with ubiquitin biology with a generate Affilins against.
toxin–Affilin® conjugate. “Our Affilin® business model has three arms. We are
Dr. Henning Afflerbach
“The Affilin® part of the conjugate recognizes looking to create technology partnerships where we iden-
Chief Business Officer
biomarkers that are specific to the cancer cell surface tify Affilin® molecules that will bind to disease-related
and binds to them. Once bound the whole complex gets targets brought to us by the partner. We also envisage E-mail: email@example.com
internalized. Inside the cell the toxin is released from establishing product partnerships where we out-license
the Affilin® through proteolytic cleavage by a cancer late stage Affilin®-based therapeutic candidates that we Contract Manufacturing
cell-specific protease that is massively over expressed in have developed. We are also interested in establishing Dr. Ole Fuetterer
cancer cells. On release, the toxin kills the cancer cell. strategic partnerships which would sustain an influx of Director Business Development
This principle has been shown to work and has been novel targets and revenues,” added Afflerbach. E-mail: firstname.lastname@example.org
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w w w.menarini.com
Armed with a promising antibody-based vaccine Slade believes that being a medium-sized private
against ovarian cancer, Menarini Group, a privately pharma company, Menarini is able to make decisions
held fully integrated pharmaceutical company head- quickly and its partners are unlikely to be victims of
quartered in Florence, Italy, is poised to enter the US research strategy changes. "We take every investment
market for the first time and has ambitions to become made very seriously and have to develop all clinical
a major player in the biologicals field. assets as quickly as we can," he added.
Recognizing the challenge of trying to grow a Krista says he is delighted with how Menarini
presence through organic growth alone, Menarini has developed abagovomab clinically. "Recruitment
is now looking for partners from whom it can in- of such patients is not easy, certainly not for a small
license and acquire promising development phase biotech, and any time it looked like they might be
speciality medicines. falling behind in their enrolment Menarini enlarged
Over the past decade, Menarini has seen its rev- the number of hospitals and cranked up the adver-
enues grow from €1.31 billion in 2000 to €2.63 bil- tising to principal investigators. They went all out
lion in 2008. Andrew Slade, President of Menarini to meet the deadlines," he added.
Biotech, now has ambitions to see a similar pattern The Phase II/III MIMOSA trial involves 870
of growth in the coming years using a double-edged patients in 151 different treatment centers in nine
strategy of developing home-grown and in-licensed countries. "We started recruiting patients in December
products, especially in biologics. 2006 and completed enrolment on time in December
"While we are not diminishing the importance of 2008. The first efficacy results are expected at the
small molecules we are most interested in expanding end of 2010," added Angela Capriati, Menarini's
our biologics pipeline because we think there is great clinical director.
medical need in this area. We have everything that is "We would like to replicate the abagovomab
needed to get biologics into the marketplace: biology, experience with other compounds and companies,"
analytical, regulatory and development/manufacturing noted Carlo Alberto Maggi, Menarini's R&D Director.
experience and financial resources," said Slade. However, Menarini is prepared to be as flexible as
Slade is looking at two potential sources of inno- necessary to get a deal done. "If a US company has
vative products. One group is European companies aspirations to establishing a fully integrated organi-
that have assets that need developing clinically and zation in its home market we would be quite happy
are willing to give up US rights. Alternatively, he with that so long as they leave us with Europe and
envisages potential deals involving US companies that other markets," he added.
have little experience or interest in commercializing Slade promises that Menarini will evaluate eve-
their assets outside North America. rything on a case-by-case basis. "We will look to
PA R T N E R I N G P R O F I L E
"We are not always looking for global rights, as align any opportunities with our existing activities
we are willing to look at appropriate regional deals," in innovative businesses and emerging markets. We
added Slade. can now demonstrate to others that we have the com-
One pillar of the growth strategy is abagovomab, petences to do what they need to do," he added.
an anti-idiotype antibody that mimics a tumor antigen Menarini employs 12,600 people, of which 740
that is highly expressed by ovarian cancer cells, which are employed in research and development.
is currently in Phase II/III trials and is being studied Maggi has a clear idea of what he is looking
for its ability to prevent the regrowth of tumors that for. "We are seeking products which have at least
occurs too often in such highly aggressive cancers. completed Phase I but, depending on the indica-
"We believe it has the potential to prevent or delay tion, we are very flexible on this point. We are
tumor relapses, in those patients who responded to looking for niche, preferably orphan indications
first-line chemotherapy, by activating an immune which have the potential for a fast track regula-
response to the cancer cells," added Slade. tory path,"he noted.
Menarini in-licensed the antibody from CellControl "We are very serious about acquiring other special-
Dr Andrew Slade
AG, a small German biotech company, in 2006. ity products which we can use to leverage abagovomab
President Menarini Biotech
"It was clear that it would be very difficult for us in the market as well as having follow-on products to
Via Tito Speri, 12 to develop the vaccine and we would need a partner. allow us to meet our goal of being a global company
00040 Pomezia (Roma) We had a number of companies looking at the data we with a US presence. We are most interested in oncol-
Tel: +39-06-91184491 generated but we chose Menarini because they have ogy, an area in which we have invested a lot of effort
Fax: +39-06-91601408 strong development and regulatory capabilities and bringing the resources into the company necessary
Cell: + 39-320-2193270 made a commitment to upgrade their manufacturing," to clinically develop and manufacture biologics in
Email: email@example.com explained Karl Krista, CellControl's founder and CEO. an oncology setting," added Slade.
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Bavarian Nordic A/S
w w w.bavarian-nordic.com
PROSTVAC™: a therapeutic cancer
vaccine showing great promise
When Bavarian Nordic acquired the rights to a thera-
BAVARIAN NORDIC A/S
Bavarian Nordic (Kvistgård, peutic prostate cancer vaccine in August 2008 as part of
Denmark) is a leading European a collaboration agreement with the U.S. National Cancer
industrial biotechnology Institute (NCI), the good news about the long-term fol-
low up of its latest Phase II trial was still months away.
company that develops and
In October of that same year, however, the Danish
produces novel vaccines for the company could announce1 that PROSTVAC™ had
treatment and prevention of life- increased median overall survival time by more than
threatening diseases with a large eight months compared with placebos among 125 men
with advanced, metastatic prostate cancer.
unmet medical need.
“To see this extent of improvement in overall sur-
Best known for its multi-million vival is very encouraging,” Philip Kantoff, Professor of
dollar agreements to supply the Medicine at Harvard Medical School and principal inves-
U.S. Government with a national tigator of the study, said at the time.
stockpile of third-generation U.S. Government contracts
smallpox vaccines, Bavarian The Danish company has won contracts of more than A pivotal Phase II trial has shown significant benefits
of PROSTVAC™ compared with placebos among men
Nordic is also moving ahead $600 million so far from the U.S. Government to develop
with advanced prostate cancer.
and produce millions of doses of IMVAMUNE®, a human
swiftly with novel cancer and
smallpox vaccine, for a national stockpile that will protect
infectious diseases vaccines. the U.S. population in case of a future biological attack. Eight months survival benefit
While biodefense is an important segment of Results of PROSTVAC™ trials have been highly promis-
Bavarian Nordic’s product portfolio, it certainly is not the ing. In all, PROSTVAC™ has undergone thirteen final-
only one. Using its specialized expertise, the company is ized Phase I and Phase II studies to date, with five more
moving ahead with a pipeline of novel therapeutic and ongoing.
Today, PROSTVAC™ is the prophylactic vaccine candidates against various cancers The most conclusive Phase II study to date was a
and infectious diseases. double-blind, randomized, placebo-controlled (2:1)
company’s most advanced
prospective Phase II study that enrolled 125 patients
therapeutic cancer vaccine Seven shots and a “ready to use” vaccine with advanced prostate cancer2.
candidate. Developed with the Prostate cancer is the second leading cancer-related cause After four years of follow-up, patients who had
U.S. National Cancer Institute to of death in American men, with an estimated 27,000 fatal received PROSTVAC™ turned out to live significantly
outcomes in the U.S this year. Today, patients with meta- longer than those in the placebo group (8.5 months
PA R T N E R I N G P R O F I L E
become a subcutaneously
static prostate cancer that is resistant to hormone therapy median overall survival added). The advantage was
injected vaccine against have just one approved treatment option: a chemotherapy highly significant (p=0.006). Importantly, PROSTVAC™
advanced prostate cancer, it has with considerable side effects, extending median overall also had a favorable safety and tolerability profile,
shown significant promise in survival by little more than 2 months. resulting in better quality of life compared with current
PROSTVAC™, made from genetically modified pox approved therapy.
Phase II studies and is expected viruses, encompasses two separate vaccines delivered In clinical trials to date, PROSTVAC™ and related
to enter Phase III in 2010. through a regimen of seven simple subcutaneous shots PSA-containing pox viral vaccines have been investi-
over the course of 6 months. gated in more than 500 patients over 10 years3.
The first shot contains a vaccinia virus modified to
encode prostate-specific antigen (PSA) and three T-cell- Phase III soon to begin
costimulatory molecules (TRICOM), which enhance A soon-to-begin Phase III trial will now need to
the specific immune response against PSA-presenting confirm these promising outcomes. If all goes well,
cells. In subsequent months, the immune response is PROSTVAC™ may significantly extend the lives of men
boosted with six follow-up shots containing a modified with metastatic, castration-resistant prostate cancer,
Jürgen Langhärig, Ph.D, MBA,
fowlpox virus that also encodes PSA and TRICOM. The for whom very limited therapy options are now avail-
VP Business Development
whole regimen is designed to create a strong cytotoxic able. With time, it may also be shown that other patient
Bavarian Nordic A/S immune response against primary and metastatic pro- groups, including those with cancers not yet resistant to
Hejreskovvej 10A static tumors. hormone therapy, can be added to the list.
DK-3490 Kvistgård Both vaccine components are recombinant viral vec-
Denmark tors, which makes PROSTVAC™ a potential off-the-shelf 1. Bavarian Nordic announcement, Oct 7, 2008
Tel: +45 33 28 83 18 product that could easily be manufactured and marketed 2. J. Clin. Oncol., 27:15s, 2009 (suppl; abstr 5013)
Email: firstname.lastname@example.org at industrial scales. 3. Expert Opinion on Investigational Drugs, 18, Issue 7 (2009)
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w w w.plexxikon.com
Plexxikon’s PLX4032 - A New Personalized
Medicine for Cancer Treatment
Plexxikon’s PLX4032 – A New PLX4032 is a novel, oral and highly selective BRAF PLX3397—Plexxikon’s Next Drug Candidate for
inhibitor that targets and destroys cancer cells har- Cancer Treatment
Personalized Medicine for Cancer boring a specific cancer-causing mutation called PLX3397 is a novel, oral investigational drug for treat-
Treatment — PLX4032 is a highly BRAF. Th is mutation is found in approximately 50% ing multiple diseases, including metastatic cancer.
selective BRAF inhibitor that targets of malignant melanomas and approximately 8% of PLX3397 is a highly selective kinase inhibitor that
all solid tumors. Together, PLX4032, and its compan- down-modulates certain immune system cells as well
and destroys cancer cells harboring
ion diagnostic to identify mutation-positive patients as certain tumor cells that promote tumor growth and
a specific cancer-causing mutation. being developed in parallel, make this an ideal per- metastases to the bone. PLX3397 is currently in Phase
Encouraging data from a Phase 1 sonalized medicine. Encouraging clinical data from 1 clinical testing for metastatic disease, and may also
extension study in mutation-positive a Phase 1 extension study in mutation-positive meta- have applicability in the treatment of autoimmune dis-
static melanoma patients showed that tumor shrink- orders such as rheumatoid arthritis.
metastatic melanoma patients age was observed in 70% of the currently evaluable
showed that tumor shrinkage was patients. Plexxikon, along with its partner Roche, Plexxikon’s Oncology Pipeline and Platform
observed in 70% of patients. has accelerated development plans for potential reg- Among others, Plexxikon’s oncology programs include
istration in melanoma with the initiation of a Phase as targets Raf, PI3K, Fms and Trk. Plexxikon is antici-
Plexxikon, with partner Roche, has 2 pivotal trial and plans to ini- pating moving another
accelerated development for tiate a Phase 3 clinical trial by compound into the clinic
potential registration in melanoma year end 2009. from its oncology pipeline
and is conducting a Phase 2 pivotal
With a co-promote option in the
trial with plans for a Phase 3 trial by U.S. for PLX4032, and a pipe- Plexxikon’s Scaffold-Based
the end of 2009. line of additional oncology drug Drug Discovery™ plat-
candidates, Plexxikon is laying form and early develop-
the groundwork for a commer- ment capabilities have been
cial oncology franchise, while highly productive to date.
continuing its business model of The platform is particu-
CONTACT DETAILS: leveraging its discovery and early Day 0 (Baseline): Day 15:
larly amenable to design-
development platform in multi- Before Treatment After Treatment ing highly selective kinase
Kathleen Sereda Glaub ple therapeutic areas and seeking inhibitors either targeting
President co-development partners at the BRAF Mutation-Positive Patient Treated on a single kinase, or selective
Email: email@example.com early development stage. 320 Mg/BID dual inhibitors.
plexxikon.indd 1 21/12/09 09:56:31
w w w.pergamum.com
First-in-class opportunities in dermatology & wound healing
Pergamum is a new kind of biopharmaceutical com-
Pergamum focuses on the dermatology
pany focusing on the dermatology and wound healing Antimicrobial therapy —
and wound healing markets. The markets. Projects are based on highly innovative, propri- conquering microbial resistance
company has four main projects — etary technologies emanating from world-class research,
three of which are in clinical and target therapeutic indications with unmet medical The Pergamum Operating Unit, DermaGen, is develop-
PA R T N E R I N G P R O F I L E
development. All offer first-in-class needs. During development, opportunities for partner- ing a new class of treatment targeting dermatological
potential in markets with significant ships, licensing and other commercial transactions are infections. The lead product is a novel antimicrobial
unmet medical needs. Pergamum is a peptide (AMP) that has a broad spectrum of activity
Karolinska Development company. Four fi
first-in-class projects and is both bactericidal and fungicidal. Being derived
Pergamum has four main projects in its pipeline, all from an endogenous human protein there is minimal
of which offer first-in-class potential. Three projects risk of microbial resistance — opening up unique
are already in clinical phase development. Conditions
opportunities for long-term and prophylactic use. A
covered include prevention of post-surgical adhesions,
healing hard-to-heal-wounds, prevention of bacterial strong technology platform means that AMPs can be
and fungal infections, atopic dermatitis, impetigo and fine-tuned to target specific commercially interesting
infected wounds and burns. indications.
Projects are developed within focused Operating
Units. Pergamum supports these with strategic man- Promising clinical results — in a recent Phase I/IIa
agement, business development, drug development and clinical trail, targeting atopic dermatitis, the candidate
operational assistance as required. This structure provides
Jørgen Thorball, Chairman cost-efficiencies and synergistic advantages relating to
ffi drug demonstrated a significant reduction of total
both product development and commercial activities. microbes in eczemas compared to placebo. Although
Jørgen Thorball, Chairman
The recent appointment of Jørgen Thorball as Chair- the trial was not designed to show clinical efficacy, a
man and acting CEO has further strengthened Perga- trend towards improved eczema status was also seen.
Tel: +46 (0)8 52 48 91 00
mum’s capabilities. Dr. Thorball has a proven track record
in the successful development and commercialization of
Pergamum AB new products within the pharmaceutical industry.
Fogdevreten 2b, Solna Pergamum is a Karolinska Development AB com-
SE-171 77 Stockholm pany, making it part of one of the largest life science www.dermagen.se
Sweden portfolios in Europe.
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The Emergence of Integrated Partnerships
in the Preclinical CRO Industry
Pharmaceutical outsourcing industry-focused
research conducted by the Center for the Study Demand for outsourced clinical services continues to grow
of Drug Development at Tufts University (CSDD
at Tufts) indicated that while the number of phar- Contribution of Research Personnel to New Drug Development
maceutical and biotech companies with active Leading CROs
clinical projects increased by 80% — from 1,167 50000
in 2000 to about 2,100 in 2008, R&D headcounts
have remained stable (see Figure 1). Concurrently,
contract research organizations (CROs), a source 40000
Number of Personnel Worldwide
of preclinical outsourcing services, increased their
headcount by 65%, and pharmaceutical companies
and CROs are under pressure to improve R&D effi-
ciency, a situation that has been exacerbated by the
economic downturn. According to Tufts University 20000
professor Ken Getz, who studies CRO dynamics,
“Stronger, deeper partnerships between drug spon-
sors and CROs may be the key to reducing cycle 10000
time and lowering development costs.”
The traditional role of a CRO is that of a service
provider contracted by a sponsor to perform a spe- 0
2000 2002 2004 2006 2008e
cific task, such as drug optimization or toxicology Source: Tufts Center for the Study of Drug Development
screening. The attractiveness of using a particular
CRO centers on a company’s ability to perform the Figure 1. Globally, the number of companies with active clinical projects increased by 80%—from
task more quickly and less expensively than the 1,167 in 2000 to about 2,100 in 2008 — while sponsors have kept their R&D headcount’s stable. CROs
sponsor company can on its own. At one end of the made up the difference by increasing their headcount by 65%.
preclinical CRO spectrum, simply being fast and
efficient while adhering to the prevailing standards
of quality is enough. However, that business model Integrated or entangled relationships are not the company “will take on some of the risk in your
Co N T R AC T S E R V I C E S F E AT U R E
seems to be giving way to the dynamics of a rapidly unique to big players such as Covance. Smaller preclinical program.” Numerate actually guarantees
evolving supply chain. According to Getz, “The CROs are also adopting more flexible business the final product by tying their reimbursements to
historical, transactional approach to outsourcing, models. On the far end of the more-than-a-pro- success in the laboratory, clinic and market. “We
where sponsors manage the entire development vider spectrum sits Numerate, a California-based have not had a dissatisfied customer yet,” says
process but engage CROs and other service provid- preclinical CRO founded a little over a year ago. Lanza. In 2008, the company signed a partnership
ers to handle specific tasks, is giving way to more Numerate is a technology–focused platform deal with Presidio Pharmaceuticals (San Francisco,
integrated partnerships. In this new approach, both company based on a partnering business model. California, USA) an infectious disease-focused
parties interact more as equals, drawing on their “Numerate was started assuming people wanted a drug-development company. The deal was aimed
respective experiences and knowledge, enabling partner.” explains Guido Lanza, Numerate’s CEO. at developing improved versions of drugs against
them to leverage capabilities and create greater effi- Not surprisingly, Numerate repeats the mantra hepatitis C. It is hoped the partnerships like the one
ciency and flexibility to solve problems jointly.”1 of many preclinical service providers, claiming that signed with Presidio will bring in additional cash
A deal inked about two years ago between Eli it can deliver drug leads faster, cheaper and with to offset Numerate’s burn rate, as the company pur-
Lilly (Indianapolis, Indiana, USA) and Covance more predictability regarding mode of action and sues its own internally developed drug candidates.
(Princeton, New Jersey, USA), the largest publicly toxicology. What is unique is the way the company According to the CSDD at Tufts report, spon-
traded CRO, clearly illustrates the shift in the bal- goes about accomplishing this goal: it owns propri- sors and CROs expect their use of transaction-
ance of power that once routinely governed phar- etary development algorithms, has a database of based outsourcing to diminish, but not disappear,
maceutical outsourcing relationships. Covance, the known activity of 10 million compounds, and a over the next five years. The report argues that the
a company that offers both preclinical and early supercomputer. The technology platform makes it partnering approach will be augmented increas-
clinical services, purchased Eli Lilly’s research possible to describe the specific profile of a desired ingly by portfolio-based relationships. Ronald van
facilities in Greenfield, Indiana, for US$50 mil- drug and several weeks later create a handful of der Geest, Chief Development Officer of Kinesis
lion. In turn, Lilly scrapped its traditional R&D compounds the company can formulate and begin (Breda, the Netherlands), a privately owned com-
program and signed a ten-year, US$1.6 billion con- to test. Numerate’s drug design technology and pany that supplies biometric support (i.e., pharma-
tract with Covance. Covance employed about 260 drug leads were acquired from Pharmix, a separate cokinetic, statistical analysis of data from preclini-
Lilly employees and took responsibility for Lilly’s company that Lanza co-founded in 2000. Pharmix cal and clinical studies), has a different perspective
non-GLP toxicology, in vivo pharmacology, quality ran out of cash as a drug-development company. and says that there are powerful arguments in favor
control laboratory and imaging services. The deal Acquiring the Pharmix drug-engineering sys- of a continued emphasis on “straight” service rela-
also included some level of commitment for clini- tem and its early-stage drug candidates now puts tionships.
cal pharmacology, central laboratory, GLP toxicol- Numerate in a position to carry on Pharmix’s work, Kinesis is strictly a service company. “Keep it
ogy studies and clinical Phase II–IV services. Lilly but with a more sustainable business model. simple, keep it clear — so that more people find it
claimed the deal would help the company control Lanza explained that a distinct characteristic easy to work with you,” says Geest as he describes
the cost of drug development. associated with Numerate’s business model is that why he feels resting on the service side of the part-
A DV ER T I SEMENT FEAT URE
ner/service CRO continuum is optimal. “There is
still plenty of business on a service basis. Kinesis is
Drawing on his experience in pharmaceuti-
cal research, both with regulatory authorities and
industry, Kees Groen founded Kinesis in 1997 and
at the time served as its only employee. Ever since
the headcount has been increasing, growing by 30%
in 2008, while retaining profitability. The company
currently has over 40 employees.
Geest believes that there are some pitfalls to the
partner approach. He feels that ‘shared interest’ can
lead to a loss of objectivity. He also explains that
Kinesis’ management is very careful to not have
conflicts of interest “which is why we don’t risk-
share.” Interestingly, Geest questions whether the
industry is giving way to a reinvention of itself.
“Some decisions are cyclic,” he explains, “You
see one trend appearing and then the opposite.
Whether discovery is integrated or separated, the
work does not change.”
When asked whether the partnering model
highlighted in his report could be a passing thing,
Getz replied, “I couldn’t disagree more with the
notion that integrated partnerships between spon-
sors and CROs is a passing fad. Since the 1980s, A view of the Shanghai Zhangjiang Hi-Tech Park from Zuchongzhi Road. The park is home to an
sponsors and CROs have entered into transactional abundance of CRO and leading pharmaceutical companies’ R&D Centers. Photo by Baycrest.
relationships that resulted in completed work. But
Co N T R AC T S E R V I C E S F E AT U R E
they also generated out-of-scope costs, failed to
deliver efficiencies due to redundant personnel addressing every link along the pharmaceutical in Taizhou, have been set aside for life sciences,
assigned to micromanage the relationship, and supply development chain. China is in a position and these parks have provided a good deal of room
established restrictive levels of oversight. Given the to become a more integral part of the global phar- for the growth of CROs and CMOs.
volume of global work that needs to be performed maceutical industry due, in part, to the activities of The Chinese government has also undertaken
today combined with significantly limited capacity, its CROs. efforts to attract Chinese talent back from abroad
sponsors must work smarter and more efficiently The CRO industry in China originated with by improving resource levels (financial and struc-
with large highly diverse CROs and niche service chemistry services. China’s contract manufacturing tural). Top government officials from the nation’s
providers. Integrated partnerships represent an organizations (CMOs) began engaging in active science parks have also gone on the road pitching
evolutionary step in establishing more effective and pharmaceutical ingredient (API) production as to talent pools working in places such as the bio-
efficient collaborations. This trend toward higher early as the 1990s. Manufacturing may be the larg- tech hubs of San Francisco and Boston.
levels of integration has already unfolded in other est segment of the CRO market, but it is the other An ability to provide a cost advantage to the
industries such as film, telecommunications and aspects, preclinical and clinical research, that are industry has prompted the number of CROs in
financial services.” attracting new interest from abroad. China to expand substantially over the last five to
“There is no question that demand for spe- Major policy initiatives contribute to the seven years. Originally, the new generation CROs
cialized, high quality niche service providers will momentum. China’s 15-year science and technol- were founded by sea turtles — the term used for
always be there — but increasingly, these niche ogy roadmap names life sciences as an important overseas returnees. (The two words share a com-
providers will find themselves hired and managed industry for growth. The plan commits China mon pronunciation, ‘hai gui’, in Mandarin.) More
by major CROs who have entered into functional to investing 2.5% of the country’s gross domes- recently, significant financial backing (local and
and alliance based partnerships with sponsors.” tic product (GDP, estimated at US$4,607 billion foreign) has become available, therefore larger
in 2009) in research and development. Reforms CROs are emerging with leadership that may or
Heading East promote industrial development and small and may not be Chinese.
In an effort to increase productivity, large phar- medium size businesses, and provide tax breaks For example, in 2008 HD Biosciences received
maceutical companies have been looking East. for high technology zones. Additionally, China’s financing not only from an Asian high-tech backer,
This is not a new trend, but in the country that central and regional governments had been making Morningside Venture, but also from Lilly Asian
is now one of the largest outsourcing suppliers, heavy investments in life science start-ups clus- Ventures and Pfizer Venture Investments. The
China, the pace of change is rapid. A combination tered in R&D parks located in the country’s major financing marked one of the first examples (if not
of Western demand, sustained government initia- cities (Beijing, Shanghai, Suzhou, Tianjin, Taizhou the first example) of more than one pharmaceuti-
tives, and the nation’s economic boom has created a and others). Large areas (i.e., 10–15 square miles cal company taking an equity position in a China-
highly dynamic atmosphere in China’s CRO indus- or more) in R&D parks, such as in Zhangjiang based CRO. The Morningside Group was founded
try. China is now home to more than 250 CROs Hi-Tech Park in Shanghai or China Medical City in 1986 by the Chan family of Hong Kong and has
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is US$100 million. On the thicker side sit GSK and
Top TEn pHaRma Building pREclinical FaciliTiEs in cHina
Novartis. GSK is building facilities for its neuro-
• Roche opens an R&D in Shanghai representing the first R&D facility to be set up in China by a degenerative and neuroinflammatory drug-devel-
major pharmaceutical company opment programs in Puxi. According to Jingwu
• Astra Zeneca announces US$100 million for R&D investment over 3 years. Zang, head of GSK’s Research and Development
• Pfizer inaugurates an R&D center in Shanghai and pledges to spend about US$25 million over Centre in Shanghai, the growing talent pool of sci-
entists who trained overseas is one of the factors
the next five years.
that attracted GSK to build a facility there. GSK
• Sanofi Aventis opens a drug discovery facility opens in Shanghai.
plans to employ 1,000 people over the next 10
• Novartis announces intentions to open Novartis (China) Biomedical Research Co., Ltd.,its first years. Novartis recently announced a continuing
China R&D center to be located in Shanghai investment of US$1 billion into the R&D they are
• Zhangjiang High-Tech Park. Total promised investment to be US$ 98 million. conducting in China.
Two other preclinical-CRO phenomena, both
• Zhangjiang High-Tech Park announced as location for AZ Innovation Center China
palpable in China, are the increases in complexity
• GlaxoSmithKline opens an R&D centre in Shanghai to investigate neurodegenerative diseases and consolidation within the industry. The indus-
and announced plans to channel US$100 million by the end of 2008 into China-based a
try in China is becoming more complex as more
neuroscience research center
and more companies offer biological services. HD
• Roche inaugurates Pharma Development Center China (PDCC) a drug development center Biosciences’ integration of biological services is
designed to carry out all the stages of drug development.The primary budget for the center is just one example. Another flourishing company is
100 million U.S. dollars and it will target cancer and metabolic diseases. Pharmalegacy, a firm dedicated to providing bone
• Eli Lilly & Company inaugurates a Chinese R&D headquarters in the Shanghai metabolism and other disease models. Darren Ji,
• Zhangjiang Hi-tech Park and adopts an R&D management and venture capital investments Pharmalegacy’s CEO, confirms that the company’s
model to seek,promote and manage the company's cooperation with Chinese companies growth in its first year of business was “formida-
and R&D institutes. ble”. In 2008, the veteran animal-model supplier,
• Foundation completed for a 38,000 sqmfacility to house 400 Novartis researchers at Shanghai Charles River Laboratories International, Inc., see-
Zhangjiang High-Tech Park. ing the writing on the wall, opened a 60,000 square
foot preclinical facility in Shanghai. The maneuver
• Roche announces it will expand facilities at Shanghai’s Zhangjiang Hi-Tech Park. In addition,
was intended to position Charles River as the stra-
Co N T R AC T S E R V I C E S F E AT U R E
Roche has established an office for Roche Pharma Partnering in Asia at the site. The goal of
both initiatives is to discover innovative medicines in China tegic partner to its multinational pharmaceutical
clients located nearby.
• Announcing a new partnership with the Shanghai Institutes for Biological Sciences,
Consolidation through M&A is also occurring
the company will conduct work on drug discovery in the areas of cancer, diabetes and
to a significant degree. In China, Pharmaceutical
neurological disease (in China), and will put a new biometrics facility in Beijing.
Product Development (PPD) announced the
acquisition of both Excel Pharmastudies and
• AstraZeneca China breaks ground for its new site in Zhangjiang High-Tech Park. R&D to BioDuro, two prominent companies providing
focus on common Asian diseases – liver cancer, stomach cancer and esophagus cancer, by both clinical and preclinical services in China.
exploring and accumulating knowledge on Chinese patients as well as their genetic and These acquisitions made it feasible for PPD to offer
biological marks. The company will invest about US$150 million over the next five years to a full line of services from preclinical to clinical
establish an R&D center in Beijing. trials. This places PPD in contention with other
• Bayer Schering Pharma/ Bayer Healthcare announces a strategic partnership with Tsinghua companies offering a more complete range of
University, (Beijing) to establish a joint research center, the Bayer-Tsinghua (Institute of services.
Biomedicine) Research Center of Innovative Drug Discovery. In 2008, HD BioSciences, Sundia Meditech and
• Sanofi-Aventis announces plans to establish a joint laboratory of regenerative medicine with NovaSecta entered into a strategic alliance to pro-
Xuanwu Hospital of Capital Medical University in Beijing, to research senile diseases, including vide drug-discovery solutions. NovaSecta, a con-
CNS and metabolic diseases. sulting and project management company, has an
extensive client base of mid-sized pharmaceutical
and biotech companies in Europe. The alliance is
very actively invested over the last four years in ear- cal companies have preclinical development facili- an organic progression for NovaSecta’s evolution
ly-stage biotechnology and life science companies ties located in or around Shanghai (or are potential as an R&D services company for European phar-
in China. HD Biosciences specializes in conducting residents as some facilities are under construc- maceutical and biotech companies. This alliance
assay development and high-throughput screening tion). They include Roche, Novartis, Astra Zeneca, brings together the high-quality scientific capabili-
services. The funds are to be used to support the GlaxoSmithKline (GSK), Eli Lilly, Johnson and ties of HD BioSciences and Sundia with NovaSecta’s
expansion of its high-throughput screening pro- Johnson (J&J), Pfizer, Abbott and Sanofi Aventis. extensive client base.
gram and build new capabilities in in vivo biology The R&D is either performed within dedicated
and DMPK bio-analytical services. facilities or a collection of CROs are managed to Reference
Large pharmaceutical companies are experi- perform the task. Eli Lilly sits on the lean side of 1. Moving Drug Development outsourcing to a
menting within China’s dynamic CRO environ- the scale, employing a staff of about ten people Higher Level: Tufts Center for Drug Development
ment and employing a variety of drug-development dedicated to outsourcing and overseeing diabetes R&D Management Report • Page 4 Volume 4,
strategies. Nine of the world’s leading pharmaceuti- and oncology drug discovery. The five-year budget Number 3 • June 2009
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w w w.bioyong.com
A Catalyst In China’s Emerging
China’s biotechnology and pharmaceutical research collaborative partnerships for the sake of sharing both
Bioyong, a biotechnology sectors have made great strides in recent years and the research facilities and proprietary technologies. According
services company, is a growth of these prospective industries provides a clear to Li: “There are still not enough biotechnology service
example of areas where the country’s economic boom is companies in China. And, in the existing companies, the
manifestation of the Chinese
palpable. While the elements of the biotech industry and capability of the technical staff also needs to improve.
government’s desire to bridge cluster growth (i.e., the provision of capital coupled with Reliability is an attribute that is stressed throughout
the gap between academic excellent research and available lab space to grow com- Bioyong.” Li predicts that in the future there will be a
panies) are universal, every region provides its own local huge market for biotechnology services in China.
research and industrial flavor. In addition to financial support provided directly
application. While advancing by the Chinese government, close-knit collaboration Genomics and metabolomics
proprietary diagnostic and and integration of research institutions and emerging An extensive panel of genomics and biology services has
biotechnology companies has augmented the number of been offered by Bioyong, including SNP screening, len-
cloning technologies, Bioyong opportunities for advancing research and growing new tivirus/adenovirus packaging, RNAi vector construction,
provides access to state-of- innovation-based businesses in China. fluorescence real-time quantitative PCR and bioinformat-
the-art genomics, proteomics A look at Bioyong, a biotechnology services company ics. And now they are expanding their genomics services
set up with support from Peking University Investment to genome sequencing.
and metabolomics services to Alliance (PKU PE), provides some insight into the work- The genome sequencing services will be provided in
the academic research ings of China’s biotechnology industry. The PKU PE was collaboration with Yu. Yu is founder of the Beijing Institute
created to bridge venture investment and the early devel- of Genomics. The idea for a new institute was created in
opment of academic projects with market potential. 1998 to conduct the research providing China’s contribu-
Primarily based in the Beijing Zhongguancun High tion to the International Human Genome Project (HGP).
Tech Park, Bioyong is a young company that is fostering Yu applied his previous experience from University of
the advancement of biotechnology and pharmaceutical Washington Genome Center where he worked on human
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research and the growth of emerging biotechnology com- chromosome 7 for the HGP. He brought a part of the
panies by providing state-of-the-art technical service plat- HGP back to China (known as the “1% Project” which
forms for biotechnology research. Entrenched with lead- was completed in 2001, two years earlier than anticipat-
ing members of the biotechnology research community ed), with the encouragement by his mentor Maynard V.
of China, Bioyong has been offering services that include Olson, who is one of the major architects for the Project.
genomics, proteomics, bioinformatics and, the relatively The Institute has gone on to complete the sequencing of
new technology on the block, metabolomics. Several of other major genome projects, such as the Superhybrid
Bioyong’s clients, including Peking University, Tsinghua Rice Genome Project, the Silkworm Genome Project, and
University, China Agricultural University, Chinese PLA the Chicken Genome Diversity Project.
General Hospital, Peking Union Medical College Hospital, Another aspect of Bioyong’s service offerings, metabo-
and Shanghai Rui Jin Hospital, are working to make the lomics, has emerged as a key technology in pharmaceu-
transition from research innovation to market applica- tical discovery and development. This system biology
tion. approach is evolving to be the small molecule counterpart
SPE-C nano-magnetic beads: Based on
weak positive ion-exchange theory, from Behind some of Bioyong’s extensive service offerings of proteomics. Metabolomics provides an in vivo meta-
biological samples (serum, saliva, pleural are a formidable handful of leading research scientists bolic profile that can provide information on drug toxic-
fluid, plasma, urine, lymph, cerebrospinal with international experience in applicable areas of ity, disease processes and gene function at several stages
fluid, tears, cell supernatant, cell lysis
buffer, etc.), the beads can capture small expertise. The list includes Ning Li, a professor at China in the discovery-and-development process. Qingwei Ma,
molecules and low-abundance proteins Agriculture University, Jun Yu, a professor and Associate the founder and CEO of Bioyong, added the technology
and peptides, which can then be used Director of Beijing Institute of Genomics, Chinese to the service offerings in response to a growing interest
directly for matrix-assisted laser Academy of Sciences (CAS), and Yaping Tian, Director in the research community.
spectrometry (ABI, Bruker, Shimadzu, of the Department of Clinical Biochemistry, Chinese PLA
SAI, Waters, PE) analysis. General Hospital. Because of their significant contribu- Proteomics and serum polypeptide-
tions to biology, these leading investigators have all gained spectrum technology
recognition in the biology community. For example, Li To enhance its proteomics services, Bioyong formed a
1. Capture many kinds of low- became one of the youngest members of the Chinese partnership with the Beijing National Proteome Research
abundance proteins/peptides to
ensure specificity of the system Academy of Engineering owing to advances in animal Center. “This is a strong alliance and as a result of this
2. Simple and quick operation cloning attributable to his research; Yu in 2002 received cooperation, Bioyong can provide a progressive panel of
3. Superior reproducibility due to huge the Scientific American Research Leader of the Year award proteomic solutions,” says Ma, who developed the service
surface area of the nano-magnetic
owing to his significant contribution to sequencing the because he identified a burgeoning need in the research
4. Suitable for high throughput rice genome. Li, Yu, and Tian were originally Bioyong’s community. Bioyong’s proteomics services include the
5. Cost effective loyal customers but their relationship has evolved into discovery of proteins and the identification of differ-
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ences in protein profiles using liquid-protein chip finger-
print analysis, two-dimensional gel electrophoresis, and
shotgun proteomics. Shotgun proteomics is named for its
DNA sequencing counterpart. This method of identifying
proteins uses a combination of high-performance liquid
chromatography and mass spectrometry. The proteins
in the mixture under investigation are digested and the
resulting peptides separated using liquid chromatography.
A mass spectrometer is then used to identify the peptides
and create a proteomic profile. Bioyong also offers matrix-
assisted laser desorption ionization – or MALDI – a mass
spectrometry imaging technique that involves the visuali-
zation of the spatial distribution of proteins, peptides, drug
candidate compounds, and their metabolites, biomarkers,
or other chemicals within thin slices of sample.
Mass spectrometry is an integral part of Bioyong’s
unique service offerings and proprietary research. “Using
mass spectrometry, we can obtain a high-resolution analy-
sis of the healthy condition of the human body,” explains
Dr. Yaping Tian, the Director of the Department of Clinical Main interface of the BioExplorer software: The interface consists of the mass spectrum (top
Biochemistry, Chinese PLA General Hospital, and a cli- left), the virtual gel map (bottom left), a sample table (top-right), a sample comparison chart
ent and collaborator of Bioyong. “Now diagnosis depends displaying the mean values and standard variations of two selected protein peaks (bottom
right), and the classification model selection window (forefront). BioExplorer is integrated with
more and more on large-scale medical diagnostic equip-
the Support Vector Machine (SVM), Fisher’s Discriminant Analysis, and Radial Basis Function
ment.” Tian’s research interests involve the identification
neural network algorithms. The software establishes an early warning model of high accuracy by
of biomarkers for early diagnosis and prevention, and he selecting differential proteins through data mining algorithms after sample pretreatment.
is attempting to find them using mass spectrometry-based
signatures aided by serum polypeptide-spectrum technol- ner of Bioyong, took an interest in animal cloning in 1996,
ogy. the year Dolly the sheep was born in the United Kingdom.
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Serum polypeptide-spectrum technology can be used Li brought the standard of somatic cell cloning technology
to find protein markers for early tumor diagnosis. By com- in China to a new level when he returned after conducting
paring the spectrum of proteins in patients at various research in several world-renowned animal biotechnology
stages of the disease and detecting and analyzing the cor- laboratories in Germany, Japan, and the United States. Li
responding changes in the protein profile, one can observe started by cloning a cow and then applied the technology
characteristics and chart the pathology. The information to pigs. More recently, Li turned his attention to the issue
can be used in early diagnosis, drug efficacy monitoring, of infant nutrition by breeding a cow genetically modified
and eventually to find a new drug target, and to design to produce milk with high levels of human lactoferrin.
a new drug based on the profile. To this end, Bioyong Lactoferrin is an important antimicrobial protein found
has detected and analyzed the polypeptide-spectrum in in breast milk that can help to improve a baby’s immunity.
thousands of serum samples for its clients. Cow’s milk expressing human lactoferrin can serve as a
To sustain its growth, Bioyong has put a lot of effort replacement for human breast milk. Li expects that in the An example of the BioExplorer two-
into developing proprietary innovations in instrumenta- next 3 to 5 years the product will be able to enter the mar- dimensional (top) and three-dimensional
tion, reagents and bioinformatics. Such innovations are ket. Li also has succeeded in genetically engineering cows display (bottom) of the differential
often customized according to the needs of a client. “To to express two additional human milk proteins, lysozyme protein peaks. The color (red or green)
grasp the initiative of the market, we perform R&D and and lacoalbumin. represents two differential sample groups.
innovate continuously in order to hold our own intel- Transgenic animals (a subset of genetically modified
lectual property. It’s the only way to have sustainable organisms which have inserted DNA that originated in a
development,” said Ma. Bioyong applied for a total of 13 different species) and the use of transgenic animals for
patents last year. For example, BioExplorer, a bioinfor- the expression of pharmaceuticals are a major part of the
matics software system developed by Bioyong, facilitates Chinese “863” plan, a program funded and administered
their serum polypeptide-spectrum analysis services, and by the government of the People’s Republic of China. The CONTACT DETAILS:
SPE-C nanomagnetic beads have superior performance 863 plan, so named because it was incepted in the third Bioyong
for capturing small molecules, low-abundance proteins month of 1986, is intended to stimulate the development No.901, Unit 2,Tower C, Longrange Bldg.
and peptides in biological samples. of advanced technologies in a wide range of fields for HaiDian District, Beijing
the purpose of rendering China independent of finan- P. R. China
Ning Li and pharming cial obligations for foreign technologies. Li says: “The
The portmanteau, pharming (a combination of pharma- next step for our somatic cell cloning is to strengthen the Tel: 86-10-82609511 82608397 82608582
ceutical and farming) refers to the use of genetic engineer- industrial capabilities of genetically engineered animals. Fax: 86-10-82608397 ext.625
ing to insert genes that code for useful pharmaceuticals Bioyong will be one of our very important collaborators firstname.lastname@example.org
into host animals or plants. Li, a long-time client and part- in this endeavor.” www.bioyong.com
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w w w.biofocus.com
BioFocus provides large and small biopharma companies in contract research, which is a vibrant and focused field.
BioFocus, headquartered near and non-profit organizations access to a comprehensive suite To be successful in drug discovery needs strengths in the
of discovery products and services. These cover all stages triangle of chemistry, biology and pharmacokinetics – what
Cambridge in the UK, is a
of the drug discovery process, from target identification to the molecule is, what the molecule does to the organism and
vibrant and cutting-edge therapeutic candidate, as well as compound management what the organism does to the molecule. I believe that in
contract research organization services, and are available separately or as part of an inte- our offerings and technologies we have one of the strongest
grated drug discovery solution. examples of this triangle.
supplying drug discovery
We also provide companies with access to the latest tech-
products and services from Q: What can BioFocus offer that an in-house nologies through our close links with our partners, including
target to candidate. It employs discovery group cannot? Cresset BioMolecular, which has developed molecular field
We can support companies by providing cost-effective ser- software; ZoBio, which has a highly sensitive NMR screening
250 people and has research vices, from a single technology to an entire, integrated, drug platform; Oncodesign, which specializes in oncology drug
facilities in the UK, the US, the discovery program. We offer access to suites of technologies discovery; and Optibrium, our first spin-out company, with
Netherlands and Switzerland, that our clients may use infrequently, obviating the need to its StarDrop™ in silico optimization platform.
invest in-house. For example, few companies want to cre-
and sales offices in Tokyo and ate a structural-biology section to elucidate the structure Q: Which is BioFocus’ most exciting
Singapore. BioFocus was of a single protein, or set up a natural-product division to technology?
develop an individual product candidate. Our adenoviral target discovery technology was the found-
founded in 1997 and acquired
We have a very broad offering, and we have to be as ing technology for our group. It allows us to knock-down
by Galapagos in 2005, and is good as, or better than, in-house research because our clients or knock-in single genes of interest, reducing or increasing
now the biotechnology demand it, and we live in a competitive and fast-moving levels of proteins produced. This gives us an idea of the effect
marketplace. of a drug directed to that particular target. BioFocus and its
company’s service division. parent company, Galapagos, have signed a number of agree-
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Q: What kinds of companies outsource drug ments for this technology, including with GlaxoSmithKline,
discovery? Lilly, Johnson & Johnson, and Merck & Co.
• Integrated drug discovery – gene to
All kinds! Our customers fall into four categories, and we Our fragment-based drug design technology is a rela-
candidate drug discovery programs
find that they all have different needs. tively new offering and is very exciting. This allows us to
• Target discovery – using human
primary cells Big pharma companies have large in-house R&D depart- identify the fragments that bind to a drug target, which can
• Assay development and screening – ments but are looking for access to novel targets and flexibil- then be optimized into potential leads and can also include
using tailored biochemical and cellular ity in drug discovery and so will use us for the more specialist ZoBio’s Target Immobilized NMR Screening (TINS) technol-
assays processes. These include natural-product discovery, struc- ogy, which allows rapid screening at very high sensitivity.
• Fragment-based drug discovery tural biology, fragment-based screening and target discovery
• Structural biology – using X-ray using our adenoviral platform. Q: Which was BioFocus’ most exciting
crystallography and NMR Mid-size companies tend to have smaller in-house R&D collaboration?
• In silico drug discovery – accelerating departments, so will use us as a supplemental resource, We signed a significant drug discovery service contract with
discovery with computational employing our more generic capabilities, such as medicinal UCB in 2008, based around an undisclosed enzyme. This is
chemistry and biological screening. an interesting medicinal-chemistry project working on an
• Medicinal chemistry – designing and
synthesizing novel candidates Biotechnology companies are often virtual, and use us unusual target, and we have created an active series of lead
to gain access to our research scientists and their expertise. compounds with good potential.
• ADME/PK laboratory – performing
comprehensive analysis They are less likely to use us for target-finding as they usually We have been working on an oncology target discovery
• Compound libraries – synthetic and know which protein they are focusing upon. Most often, they program with Johnson & Johnson, using our adenoviral
natural for high-throughput screening use our generic capabilities, including screening, hit-to-lead technology, since 2008. We have had to devise highly sensi-
• Compound management – acquiring, optimization and structural biology. tive cellular assays for this project – this project has been
managing and distributing collections And finally, government and non-government organiza- scientifically very exciting.
tions and charities are generally completely virtual and do Both of these projects will be completed during 2010.
not have any in-house research, and so will use our integrat-
CONTACT DETAILS: ed drug discovery service, which covers the entire process Q: Where next for BioFocus?
BioFocus from target screening to compound management. We want to maintain BioFocus as a successful and sustain-
Chesterford Research Park able business in a fast-moving environment, and offer our
Chesterford Park, Little Chesterford Q: What makes BioFocus different to other collaborators access to the most experienced people and
Saffron Walden, Essex CB10 1XL, UK drug discovery companies? the best technologies in the industry to support their drug
www.biofocus.com We are one of the most experienced companies in our field, discovery endeavors. In addition, we intend to exploit new
Tel: +44 (0)1799 533 500 and we have some great people, many of whom have come relationships in the Asia–Pacific and developing nation
Email: email@example.com from big pharma but have also gained an edge from working markets.
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w w w.pharmidex.com
Fast-forwarding drug discovery
Pharmidex is unique in its focus on central nervous these, under a collaborative agreement with Genzyme
Pharmidex delivers world- system (CNS) drug-discovery and development ser- Pharmaceuticals, is Cerense . According to Dr Peter
leading CNS and ADMET vices, and has world-leading expertise and technolo- Hoffmann, Vice President of New Technology at
solutions to support gies in this field. Today the company has diversified Genzyme Pharmaceuticals, Cerense oligoglycero-
to provide a wider range of platform technologies, lipids can deliver compounds up to 250,000 daltons,
preclinical drug discovery and including in vitro and in vivo absorption, distribution, including proteins, across the BBB.
development in CNS and metabolism and excretion (ADME), pharmacokinet- To strengthen its predictive offering Pharmidex, in
ics, bioanalysis, safety pharmacology, in vitro pharma- collaboration with major players in the field, is work-
other disease areas. cology, and efficacy and safety studies. ing on the development of highly robust BBB screening
Gary Manchee, Global Head of Business Develop- models using exclusive novel cell lines and validated by
ment at Pharmidex, and previously director of drug NeuroPK® and NeuroPD™ studies.
Pharmidex offers: metabolism and pharmacokinetics (DMPK) at
• CNS solutions — GlaxoSmithKline, says: “The broadening of our offer ADMET, PK and bioanalytical solutions
assessment of brain is a natural development for Pharmidex and provides Pharmidex provides technologies to understand the
penetrability and distribution clients with a strong scientific rationale for compound link between drug level and drug effect in preclini-
of CNS therapeutics progression into drug development, ultimately cal animal models (PKPD) while balancing ADMET/
saving time and money prior to, and during, clinical PK properties, which aids in the selection of the most
• ADMET solutions —
evaluation.” appropriate drugs for clinical evaluation.
therapeutics using preclinical Pharmidex offers drug-discovery and development Pharmidex uses an extensive range of in vitro and
and human prediction data solutions in three key areas: CNS drug-discovery and in vivo ADMET technologies together with human
delivery solutions; ADMET, PK and bioanalytical solu- extrapolation science to rapidly select those molecules
• Bioanalytical solutions — tions; and collaboration and consultancy. that are more optimised for development purposes and
determination of small and possessing a greater probability of clinical success.
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large molecules and CNS drug-discovery and delivery solutions Together with a wealth of knowledge and experi-
biomarkers in tissues and Pharmidex is the only company in the world that offers ence in CNS, cardiovascular, respiratory and inflam-
direct assessment of brain penetrability and concentra- matory discovery programs, Pharmidex can aid more
• Drug delivery — tion of free compounds in the extracellular fluid. rapid progression and improvement in the probability
formulation technology “We started Pharmidex to address the main obsta- of success of potential new medicines.
delivering drugs across the BBB cles that blocked the successful development of CNS
• Free consultancy — medicines,” says Dr Mohammad Alavijeh, co-founder Collaboration and consultancy
support in drug discovery and and Managing Director. “These were the absence of The knowledge and experience of the staff at
development robust predictive models, the inability to get most Pharmidex, combined with its cost-effective platform
• Collaboration — compounds across the blood–brain barrier (BBB) and technologies and high-quality data, can help to move
partnering ongoing programs the inability to accurately assess their action when they drug-development programs quickly and cost-effec-
did cross into the cerebral spinal fluid.” tively through preclinical development. This can be
Pharmidex aims to offer a total ‘blood–brain bar- through collaborations, under a shared risk–shared
CONTACT DETAILS: rier package’ — prediction, assessment and delivery. reward model or on a consultancy basis.
The company’s unique technology platforms include Arrow Therapeutics, founded by Ken Powell, was
direct assessment of levels of therapeutic agent in the Pharmidex’s first client in 2003, and the company,
72 New Bond Street
blood and brain (NeuroPK®), measurement of neuro- now part of AstraZeneca, is still one of Pharmidex’s
London, W1S 1RR
chemical markers of therapeutic activity in the brain clients. Ken Powell was so impressed by the qual-
(NeuroPD™), and measurement of CNS side-effect ity of the Pharmidex offering that he has joined the
Tel: +44 (0)870 240 5978 profiles (NeuroTox™). These have their origins in the board as Chair. “Pharmidex has consistently provided
firstname.lastname@example.org work conducted by Alavijeh's research into the damp- high-quality data and very rapid turnaround times to
www.pharmidex.com ened efficacy of anti-epileptic drugs at the National clients, and continues to grow through offering effi-
Hospital for Neurology and Neurosurgery (Institute cient, cost-effective support and consistent delivery,”
of Neurology, Queen’s Square, London, UK). This says Powell.
11722-J Sorrento Valley Road
research led to the development of a highly innovative “Pharmidex will succeed as a broad-based pre-
technique for neuropharmacokinetic measurements to clinical services provider, with unique CNS exper-
San Diego, CA 92121 elucidate drug distribution in different brain regions. tise, because of our unequalled ability to combine
USA With a highly qualified team and state-of-the-art scientific capabilities with extensive drug-discovery
Tel: +1-858-764-1816 assessment technologies in place, 2010 will be the expertise. Clients get real value for money in terms of
email@example.com year that Pharmidex intends to focus on developing quality, cost and study design,” concludes Dr Chishty
www.pharmidex.com a range of delivery options. The most advanced of (Pharmidex Head of Science).
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w w w.pharmalegac y.com
PharmaLegacy: Championing the
Growth of Preclinical Services in China
One year after opening its doors, PharmaLegacy, the ogy, molecular pharmacology and pharmacokinetic and
PharmaLegacy is a new leading preclinical service company with a Shanghai pharmacodynamic assays, as well as preliminary toxi-
company postured to play address, boasts an international client base and a 60 per- cology screening. Though a young company, the leader-
a progressive role in China’s cent proposal acceptance rate. Their 20 clients include ship has effectively developed a robust research platform
large pharmaceutical companies as well as small and that integrates a great deal of experience with methods
fast-growing pharmaceutical medium enterprises. for validating the pharmacological effects of drug can-
contract resource industry. The rapid financial growth observed in didates and testing orthopedic devices for efficacy and
PharmaLegacy’s first-year of business may be explained, biocompatibility. About 15% of company employees
at least in part, by PharmaLegacy’s alignment with two were either thought leaders or worked for many years in
major trends expanding the outsourcing industry. The the US and European pharmaceutical industry in their
ubiquitous need for companies to control the cost of respective fields. PharmaLegacy specializes in providing
drug development and improve efficiency has prompt- the research and development to support investigatory
ed continued growth of the outsourcing industry as a new drug or device evaluation applications to national
whole. CEO Darren Ji explains, “PharmaLegacy provides regulatory agencies throughout the world.
a unique value proposition to clients. Pharmacology Though located in the Zhangjiang High-Technology
studies in animals demand a high level of expertise and Park in Shanghai, China, Ji says technology shortens the
specialized knowledge to deliver reliable and consistent distance between the facility and foreign clients. Seventy
results. Our company is able to provide these services cameras are installed in the facility’s animal and surgery
while reducing the cost of early stage development and rooms. This makes it possible for clients to observe pro-
shortening turnaround times. These advantages com- cedures in real-time through the use of video-streaming.
bined with adherence to a world-class quality standard Enabling clients to observe or even supervise during
make PharmaLegacy an attractive service provider.” procedures “adds an extra layer of assurance for the cli-
Ji realized he could take months off a project’s ent and can help when trying to understand the result,”
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turnaround time by streamlining the proposal proc- according to Ji.
ess and implementing the proposal upon acceptance. PharmaLegacy continually strives to integrate rapid
PharmaLegacy maintains a staff count that is at least service and cost savings into a system that assures a rig-
PharmaLegacy uses videostreaming 20-30 percent larger than what is needed to service cur- orously high standard of quality. All operations are based
technology in order to enable clients to rent clients. “This is done with no extra cost to the cus- on Good Laboratory Practice (GLP) standards and
observe procedures in real time from
anywhere in the world. tomer,” he emphasizes. Potential clients can expect an Standard Operating Procedures (SOP). Representatives
initial response within 24 hours of making an enquiry. from eight of the top 20 pharmaceutical and biotech
Additional cost savings come with being very clear companies have inspected and accredited the facilities.
about what is spent. Using an elaborate financial control Six of them have started working with PharmaLegacy.
system, all laboratory costs are tracked and calculated As these potential clients came to inspect, opinions on
down to the single digit and the information is retriev- optimizing operations were sought. One multinational
able on any given day. “Our project cost management corporation representative paid PharmaLegacy’s man-
system enables us to provide to our clients the highest agement the ultimate compliment saying, “Many people
value for their project dollars.” Ji explains. can set up a nice facility like this, but you guys seem to
Another major trend in the outsourcing industry, know how to run it.”
described by Ken Getz of the Tufts Center for the Study Recently, PharmaLegacy received an accreditation
of Drug Development, characterizes service providers to from the International Association for Assessment and
the pharmaceutical and biotech industry as more often Accreditation for Laboratory Animal Care (AAALAC).
becoming valued strategic partners. When discussing The established animal pharmacology models provided
PharmaLegacy, Ji illustrates this trend. “Outsourcing by PharmaLegacy include rodents, dogs, mini-pigs,
CONTACT DETAILS: needs for drug development have become more sophis- sheep/goats and non-human primates. An AAALAC
ticated. Sponsors look for more than just a pair of hands accreditation means the institution is serious about set-
to do the work. They need the service providers to par- ting, achieving, and maintaining high standards for ani-
Building 7, 388 Jialilue Road
ticipate in the work design, data interpretation and trou- mal care and use in science.
Zhangjiang High-Tech Park
ble shooting. Essentially the suppliers become intellec- Within one year, PharmaLegacy has become a very
Shanghai 201203 tual contributors in the research process. This is where attractive service provider that stands postured to con-
China specialty expertise like ours comes into play.” tinue growing. The company is actively recruiting tech-
Tel: +(86) 21-6100 2280 PharmaLegacy’s expertise is focused in the areas of nical talent from overseas. Those who are both passion-
Tel: +1 513 276 4645 (24 hour service) bone metabolism, orthopedic research and tissue engi- ate about providing outsourcing services and willing to
firstname.lastname@example.org neering, immune diseases, inflammation, and oncology. take part in charting a course for the company’s future
www.pharmalegacy.com The company provides efficacy studies, histopathol- are encouraged to apply.
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InvivoSciences LLC InvivoSciences LLC
www.invivosciences.com Discovery with a Human Touch
InvivoSciences Brings a New Dimension to Drug Discovery
InvivoSciences LLC (IVS) provides a three-dimensional including human cytomegalovirus,” Wakatsuki continued.
InvivoSciences (IVS) have (3D), tissue-based, high-throughput, high-content
combined three-dimensional (3D) physiological-profiling system for the pharmaceutical IVS’s cosmetic corporate partner has applied the tech-
human-cell cultures with high- and biotech industries. “Our products consist of liv- nology to predict the efficacy of investigative agents to
throughput screening to provide a ing tissue constructs and we can quantify their physi- improve elasticity of the skin and potential toxicity.
powerful system for addressing ological responses to pharmaceuticals, environmental
stresses, and biological agents such as virus”, explains The system can also be applied to drug and disease tar-
questions about toxicity,
Dr. Wakatsuki, co-founder and CSO of IVS. The com- get discovery. The National Institutes of Health recently
therapeutic benefit and even pany’s globally patented proprietary device Palpator™ funded a collaboration between IVS and the Medical
genetic variation. The technology assesses tissue mechanics as well as optical readouts of College of Wisconsin to identify and develop drug can-
developed by the founders can physiological parameters, and combining this device didates to reverse or at least slow the expansion of fibrotic
best be described as high- with a 3D tissue model derived from human cells results scar tissues caused by cardiac infraction. Screening for
throughput physiology. By in a highly sensitive platform for predicting toxicity, candidates will be assayed using the Palpator system and
quantifying the body’s response therapeutic benefit, and the pharmacogenomic effects of a 3D tissue model that mimics spontaneously contractile
to biologic therapies, this drug candidates. cardiac heart muscle.
company takes some of the guess-
The platform is adaptable to various tissue types, including 3D models can be fabricated using human cells or pluri-
work out of drug development. connective, skin, and heart muscle tissues. Custom assays potent stem cells; therefore, the model can also be applied
designed by IVS’s scientists provide a closer approximation to measuring the influence of DNA polymorphisms on
to in vivo conditions compared with the industry-standard the efficacy of a drug candidate. Drug discovery and
CONTACT DETAILS: two-dimensional cultures. “In two-dimensional cell culture treatment can be personalized during the preclinical
systems the mechanical microenvironment of cells departs phase. Animal model-based drug discovery is incapable
Ayla Annac, CEO, Co-Founder critically from the normal condition,” describes Dr. Elson, of addressing this critical need. IVS’s intellectual prop-
InvivoSciences LLC co-founder and Alumni Endowed Professor at Washington erty extends to drug discovery. Currently IVS is opti-
10437 Innovation Drive, Suite 172 University. IVS developed a 3D cell culture system to mizing and validating their human tissue model-based
Wauwatosa, WI 53226, USA address this limitation. “We were pleasantly surprised by technologies for quickly screening and identifying drugs
Tel: 1 800 930 9838 the recent finding that the tissue mechanics are significantly that are effective at delivering to individuals cancer che-
Email: email@example.com altered in three-dimensional culture by viral infections, motherapy with minimal cardiac toxicity.
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