Strategic Alliances
We are committed to retaining significant equity
in the value of the company's pipeline and product
candidates. Our strategy is to leverage the strength
of our extensive data and the broad potential of
our development compounds to establish strategic
alliances that provide access to complementary technology
and expertise and create near-term revenue, while
reducing our risk of product failure and retaining
long-term rights to those compounds that succeed.
These alliances provide significant support for our
internal development programs and open the door to
additional product opportunities.
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Bristol-Myers Squibb Company
Mechanism of Action
Collaboration
In September 1999,
Exelixis and Bristol-Myers Squibb (BMS) initiated
a research collaboration utilizing Exelixis' expertise
in model systems genetics to identify novel, validated
targets for new drugs. As part of the collaboration,
BMS and Exelixis share certain core technologies
and lead optimization responsibilities. BMS transferred
to Exelixis combinatorial chemistry hardware and
software, along with related intellectual property
rights. In return, Exelixis granted BMS a limited
sublicense to use Exelixis' proprietary worm (C. elegans)
and fly (D. melanogaster)
technology. This alliance provided Exelixis with
significant combinatorial chemistry assets that
today play a significant role in Exelixis' rapid
and rigorous drug candidate screening process.
Cancer Alliance
In July 2001, Exelixis established
a broad collaboration and licensing agreement with
Bristol-Myers Squibb (BMS) to create a new generation
of potential cancer drugs that selectively target
cells that harbor defects in tumor suppressor gene
pathways. Exelixis identifies and validates molecular
targets in model systems, and BMS further validates
these targets in human models. Each company has
exclusive worldwide rights to half of the validated
targets arising from the collaboration. As part of
the collaboration, Exelixis received an exclusive
worldwide license to develop and commercialize a
selected analogue of the BMS anticancer compound,
Rebeccamycin, now XL119 (becatecarin). XL119 is in
Phase III clinical trials and was out-licensed to
Helsinn Healthcare S.A. for further development and
commercialization. In December 2003, Exelixis announced
the extension and expansion of its oncology research
collaboration with BMS to increase the total number
and degree of validation of cancer targets that Exelixis
will deliver to BMS.
Cardiovascular Disease Collaboration
In December 2005, Exelixis and BMS entered into a
collaboration agreement to discover, develop and commercialize
novel therapies targeted against the Liver X Receptor (LXR),
a nuclear hormone receptor implicated in a variety of
cardiovascular and metabolic disorders. Under the terms
of the collaboration, the companies will jointly identify
drug candidates that are ready for Investigational New
Drug Application-enabling studies. BMS will undertake
further preclinical development and will be responsible
for clinical development, regulatory, manufacturing and
sales/marketing activities for such compounds. Exelixis
received an up-front payment of $17.5 million and will
receive approximately $10 million per year in R&D funding
for an initial period of two years. Exelixis also may
receive development and regulatory milestones totaling
$140 million per product for up to two products from the
collaboration, as well as sales milestones and royalties
on sales of products commercialized under the collaboration.
Oncology Drug Development Collaboration
In December 2006, Exelixis and BMS entered into a worldwide collaboration to discover, develop and commercialize novel targeted therapies for the treatment of cancer. Under the collaboration, Exelixis will identify and conduct pre-clinical development of small molecule drug candidates directed against targets selected by Exelixis and BMS. From a pool of pre-clinical compounds, BMS will have the right to select up to three investigational new drug (INDs) candidates against three different targets. Following selection of a compound, BMS will lead all global development and commercialization activities, although Exelixis has the right to co-develop and co-commercialize the programs in the United States.
Under the terms of the agreement, BMS will pay to Exelixis an upfront payment of $60 million in cash. Exelixis will also receive $20 million for each of up to three different drug candidates selected by BMS at IND. The companies plan to share development costs, commercial profits and co-promotion responsibilities equally in the United States. Exelixis will also receive royalties on product sales outside of the United States. For each program selected by BMS, Exelixis may opt out of the co-development or co-promotion in the United States, in which case Exelixis would receive milestones and royalties in lieu of a U.S. profit share.
In September 2007, the agreement was extended at BMS’ request through January 12, 2009. BMS also has the option to further extend the research collaboration by an additional year. Terms of the extension include additional research funding paid to Exelixis in the amount of $7.5M.
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GlaxoSmithKline
In October 2002, Exelixis and GlaxoSmithKline (GSK)
announced the formation of a broad alliance to discover,
develop and commercialize novel therapeutics in the
areas of vascular biology, inflammatory disease and
oncology. Under the agreement, Exelixis will deliver
to GSK a number of small molecule compounds that
have met agreed upon criteria in early Phase II clinical
testing, and GSK will have the exclusive right to
select a small subset of these compounds for further
development and worldwide commercialization and manufacturing.
In January of 2005, the GSK agreement was amended so
that Exelixis will continue to work on 12 programs
(XL647, XL999, XL784, XL880, XL820, XL844, XL184 and
five earlier stage programs) while GSK retains exclusivity
rights to 32 specified targets. GSK has the right to
select from these 12 programs up to three compounds
at proof-of-concept (completion of Phase IIa clinical
development). Exelixis retains rights to all collaboration
compounds not selected
by GSK and
may work on any collaboration targets with the exception
of the 32 targets subject to GSK's exclusivity. Under
the amended agreement, GSK may pay selection milestones
up to approximately $275 million for three compounds,
additional development-related milestones and substantial
royalties on product sales. Exelixis has retained certain
co-promotion rights for these compounds in North America.
Under the amended agreement, GSK will also provide
research funding of $47.5 million over the remaining
term of the collaboration.
In July 2007, GSK opted not to exercise its option to license XL647 for further development and commercialization. As a result, Exelixis retains the right to develop and commercialize XL647 either independently or in collaboration with third parties. The company intends to move forward aggressively with the full development of this promising compound in patients with non-small cell lung cancer and potentially other indications as well.
In August 2007, GSK requested to initiate its review of XL880 before the compound reached proof-of-concept in phase 2 trials. Exelixis agreed to this request and submitted the data report to GSK in September 2007.
Following completion of the phase 2 trial of XL784 in patients with proteinuria associated with diabetic nephropathy, Exelixis submitted a data report to GSK in October 2007. Although the phase 2 trial did not meet its primary endpoint of reducing proteinuria compared with placebo in patients with proteinuria associated with diabetic nephropathy, Exelixis is continuing to analyze the data to assess whether further evaluation of the compound is warranted.
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Genentech
In June of 2005, Exelixis entered into a partnership
with Genentech for the discovery and development
of therapeutics to target cancer, inflammatory diseases,
and tissue growth and repair. Under the collaboration,
Genentech will primarily focus on generating antibodies
to proteins provided by Exelixis, and the companies
will jointly assess their utility in a variety of
cancer, inflammation and tissue repair models. Under
the terms of the collaboration, Genentech will pay
Exelixis an upfront payment and provide R&D funding
over three years, totaling $16 million. For therapeutics
developed in cancer, Exelixis will receive milestone
and royalty payments. Exelixis maintains an option
to share a portion of the costs and profits associated
with the development, manufacturing and commercialization
of products in either the tissue growth and repair
field or the inflammation field.
Co-Development Agreement
In January 2007, Exelixis announced an agreement with Genentech focused on the development of XL518, a small-molecule inhibitor of MEK. MEK, also known as mitogen activated protein kinase (MAPK) is a key component of the RAS/RAF/MEK/ERK pathway, which is frequently activated in human tumors. Inappropriate activation of the MEK/ERK pathway promotes cell growth in the absence of exogenous growth factors. It’s a common point of convergence for a variety of cancer-related signaling pathways and, as such, it has a lot of potential in treating numerous types of cancer.
Under the terms of the agreement, Exelixis will receive upfront and milestone payments totaling $40 million upon signing of the agreement and with the submission of the IND for XL518 to the FDA. Exelixis is responsible for developing XL518 or other MEK inhibitors through the end of Phase I and if Genentech exercises its option to further develop XL518, Exelixis will receive an additional payment and Genentech will be responsible for further development, including all further development costs. Exelixis has the option to co-promote in the United States along with Genentech. Exelixis has a substantial share in the marketing and commercialization costs, as well as an initial equal share in profits in the United States, which will decrease as sales increase. Exelixis will receive royalties on any sales of the product which may be commercialized outside the United States.
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Helsinn Healthcare S.A.
In June of 2005, Exelixis established a license
agreement for the further development and commercialization
of XL119 (becatecarin) with Helsinn Healthcare S.A.
Exelixis has granted to Helsinn a world-wide, royalty-bearing
license to XL119, and has retained rights to reacquire
commercial rights to XL119 for North America. Under
the terms of the license agreement, Exelixis received
an upfront payment of $4 million and will receive
up to $21 million in milestones and royalties on
sales in the rest of the world. Helsinn will assume
the cost of the Phase III program for XL119.
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Symphony
Capital Partners, L.P.
In June of 2005, Exelixis entered into a transaction
with Symphony Capital Partners, L.P. and its investors
to provide up to $80 million of committed funding
for clinical development of XL647, XL999 and XL784.
Under the terms of the agreement, Symphony Capital,
formed Symphony Evolution, Inc. (SEI), which was
initially capitalized with $40 million and holds
an option to call an additional $20 million to $40
million within one year of closing.
Symphony, through SEI, will provide funding to Exelixis,
which, in collaboration with SEI, will continue to
conduct the clinical trials for the three compounds.
Exelixis has granted a license to the intellectual
property for the three compounds to SEI, but retains
the exclusive right, through a purchase option, to
acquire SEI's equity. Under certain conditions, Exelixis
has the option to purchase at a premium price the
rights for any one of the three compounds separately,
while retaining the option to subsequently purchase
the equity of SEI and reacquire rights to the remaining
compounds. Under the collaboration with GSK, GSK
may continue to select at proof-of-concept for further
development one or more of the programs licensed
to SEI, in which case Exelixis would have to repurchase
the selected program or programs through the exercise
of the purchase option or program option. As part
of its collaboration with Exelixis, GSK has previously
agreed to increase the selection milestone payments
for compounds that it selects and that are funded
through Symphony. If Exelixis chooses not to exercise
the purchase option, SEI will retain the rights to
the compounds.
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Wyeth
In December 2005, Exelixis signed a license agreement with Wyeth Pharmaceuticals, a division of Wyeth, related to compounds targeting the farnesoid X receptor (FXR), a nuclear hormone receptor implicated in a variety of metabolic and liver disorders. The license agreement covers several small-molecule compounds that have been shown in preclinical studies to modulate the activity of FXR. Exelixis gained rights to FXR through the acquisition of X-Ceptor Therapeutics, Inc. in October 2004. Exelixis has developed a series of potent, selective synthetic FXR ligands that lower triglycerides and improve the cholesterol profile in animal models of dyslipidemia and atherosclerosis. These compounds are also highly effective in blocking disease progression in animal models of liver disorderssss.
Under the terms of the agreement, Exelixis received a $10 million upfront payment and will receive up to an additional $147.5 million in development and commercialization milestone payments, as well as royalties on the sale of products commercialized under the collaboration. Wyeth will be responsible for all further preclinical and clinical development, regulatory, manufacturing and commercialization activities for the compounds.
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Bayer CropScience
Agrinomics LLC was formed in 1999 as an equally
owned joint venture between Exelixis Plant Sciences
and Bayer CropScience to focus on research, development
and commercialization of products in the field of
agricultural functional genomics. Bayer CropScience
provided high-throughput screening, robotics, microarray
and bioinformatics technologies. Exelixis Plant Sciences
contributed its ACTTAG technology, a collection of
seeds generated using the activation tagging technique,
and expertise in molecular and cell biology. In May
2004, Exelixis purchased from Bayer CropScience its
50% interest in Agrinomics in exchange for releasing
Bayer CropScience from all future obligations under
the joint venture agreement. In addition, Exelixis
entered into a combinatorial chemistry agreement
with Bayer CropScience, and Bayer CropScience and
its affiliates entered into a number of license and
technology agreements with Agrinomics. The agreements
are directed to the use of the assets developed or
used under the collaborative research agreement.
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Renessen
In December 2002, Agrinomics established an alliance
to enhance seed oil content in commercially valuable
crops with Renessen LLC, a joint venture between
Monsanto Company and Cargill, Inc. The collaboration
combines Agrinomics' agricultural functional genomics,
high-throughput gene screening and seed trait identification,
developed at Exelixis Plant Sciences, with Renessen's
global expertise in quality trait crop development
and commercialization, with the goal of accelerating
the development of novel proprietary crops with improved
seed composition traits. This collaboration leverages
the unique capabilities of Agrinomics' powerful ACTTAG™
gene activation and selection platform to rapidly
discover and validate genes that can optimize important
seed traits in order to increase the commercial value
of many of the world's most significant agricultural
crops. In February 2005, Agrinomics entered into
an amendment to the collaboration agreement with
Renessen that expands and extends the original alliance
between Agrinomics and Renessen.
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Genoptera
In December 1999, Exelixis established
Genoptera LLC with Bayer Corporation to develop
insecticides and nematicides for crop protection.
In collaboration with Bayer, Exelixis applied its
model systems platform and assay development capabilities
to identify unique targets that may be used to develop
new, more effective broad-spectrum insecticides,
as well as nematicides. As a result of screening
targets both from novel targets as well as from determining
the MOA of an existing compound, Exelixis delivered
to Bayer numerous targets and high-throughput screening
assays that may be useful in identifying new insecticides
for which Exelixis received milestone payments. On
March 30, 2005, Exelixis and Bayer amended their
collaboration agreement, providing for an early termination
of the research term and requiring Bayer to acquire
Exelixis' 40% ownership interest in GenOptera within
six months after the date of the amendment. At
that time, Bayer, through GenOptera, will have exclusive
rights in the field of agriculture to assays, compounds
and products developed under the collaboration
and Exelixis will have exclusive rights in all other
fields. Under the terms of the Amendment, the obligations
of Bayer to fund further research cease and Exelixis
has no further obligations to perform research.
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Sankyo Company
In March 2006, Exelixis and Sankyo Company (a wholly owned subsidiary of DAIICHI SANKYO COMPANY, LIMITED) entered into a collaboration agreement to discover, develop and commercialize novel therapies targeted against the mineralocorticoid receptor (MR), a nuclear hormone receptor (NHR) implicated in a variety of cardiovascular and metabolic diseases. Two MR antagonists have already been approved by the U.S. Food and Drug Administration for the treatment of hypertension and congestive heart failure.
Under the terms of the agreement, Exelixis will receive a $20 million upfront payment upon signing of the agreement. In addition, Exelixis is entitled to receive research funding, substantial development, regulatory and commercialization milestone payments as well as double-digit royalties on the sale of any products commercialized under the collaboration. After the joint research term, Sankyo will be responsible for all further preclinical and clinical development, regulatory, manufacturing and commercialization activities for the compounds.
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