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: firstname.lastname@example.org 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: email@example.com
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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AD VE R TI SE M E N T FE AT U RE
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: firstname.lastname@example.org
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: email@example.com
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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: firstname.lastname@example.org explained Karl Krista, CellControl's founder and CEO. an oncology setting," added Slade.
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