SOUTH SAN FRANCISCO, CA -- 08/14/07 --
Cytokinetics, Incorporated
(NASDAQ: CYTK) announced today that GlaxoSmithKline (GSK) has initiated a
first-time-in-humans Phase I clinical trial of GSK-923295 in patients with
solid tumors. GSK-923295 is a small-molecule inhibitor of
centromere-associated protein E (CENP-E). As reported at the 2007 Annual
Meeting of the American Association for Cancer Research (AACR), GSK-923295
demonstrated a broad spectrum of activity against a range of human tumor
xenografts grown in nude mice, including models of colon, breast, ovarian,
lung and other tumors. The initiation of this clinical trial triggers a
milestone payment of $1 million from GSK to Cytokinetics under the terms of
the companies' strategic alliance established in June 2001.
This Phase I clinical trial is an open-label, non-randomized, dose-finding
trial designed to investigate the safety, tolerability, pharmacokinetic and
pharmacodynamic profile of GSK-923295 in patients with advanced solid
tumors. GSK-923295 is the third novel drug candidate to arise from
Cytokinetics' broad strategic alliance with GSK.
"We are pleased that GlaxoSmithKline has advanced GSK-923295 into clinical
trials. Based on the broad anti-cancer activity we have seen in
pre-clinical models, we are looking forward to evaluating the potential
anti-cancer activity in humans for this novel drug candidate," stated Dr.
Andrew A. Wolff, Cytokinetics' Senior Vice President of Clinical Research
and Development and Chief Medical Officer.
"The initiation of this Phase I clinical trial is further evidence of
Cytokinetics' and GSK's commitment to build a solid scientific and clinical
foundation for next-generation approaches to anti-cancer therapies," stated
Robert I. Blum, Cytokinetics' President and CEO. "This drug candidate,
along with others we are developing for the potential treatment of cancer
and heart failure, demonstrates the productivity of Cytokinetics' research
activities which have now generated four novel drug candidates moving
towards proof-of-concept in multiple therapeutic indications."
Background on CENP-E
CENP-E plays an essential role in chromosome movement during early mitosis
and integrates mitotic spindle mechanics with regulators of the mitotic
checkpoint, hence CENP-E is directly involved in coupling the mechanics of
mitosis with the mitotic checkpoint signaling machinery, regulating
cell-cycle transition from metaphase to anaphase. CENP-E is also essential
for prometaphase chromosome movements that contribute to metaphase
chromosome alignment. These processes are essential to cell proliferation.
CENP-E is expressed exclusively in proliferating cells and is abundant
during mitosis; it is absent from non-proliferating cells, including
neurons. Inhibition of CENP-E induces cell cycle arrest in mitosis with
bipolar mitotic spindles and misaligned chromosomes leading to subsequent
apoptosis. GSK-923295 is the first drug candidate to enter human clinical
trials that specifically targets CENP-E.
Background on Mitotic Kinesin Inhibitors
Since their introduction over 40 years ago, anti-mitotic drugs (taxanes and
vinca alkaloids) have advanced the treatment of cancer and are commonly
used for the treatment of several tumor types. However, these drugs have
demonstrated limited treatment benefit against certain cancers. In
addition, these drugs target tubulin, a cytoskeletal protein involved not
only in mitosis and cell proliferation, but also in other important
cellular functions. Inhibition of these other cellular functions produces
dose-limiting toxicities such as peripheral neuropathy, an impairment of
peripheral nervous system function. Neuropathies are thought to result
when these drugs interfere with the dynamics of microtubule filaments that
are responsible for the long-distance transport of important cellular
components within nerve cells.
Mitotic kinesins are essential to mitosis, and, unlike tubulin, are not
present in non-dividing cells. Cytokinetics believes that drugs that
inhibit CENP-E and other mitotic kinesins may represent the next generation
of anti-mitotic cancer drugs by arresting mitosis and cell proliferation
without impacting unrelated, normal cellular functions, thereby avoiding
many of the toxicities commonly experienced by patients treated with
existing anti-mitotic drugs.
Background on Cytokinetics and GlaxoSmithKline Strategic Alliance
In June 2001, Cytokinetics and GSK entered into a broad strategic alliance
to discover, develop and commercialize novel small molecule therapeutics
targeting mitotic kinesins for applications in the treatment of cancer and
other diseases. The strategic alliance has generated three drug candidates
in clinical development, ispinesib and SB-743921 and GSK-923295. In June
2007, Cytokinetics announced a further one-year extension of the strategic
alliance's research term, which began in June 2001, to continue activities
focused towards translational research directed to CENP-E. Under a
November 2006 amendment to its collaboration and license agreement with
GSK, Cytokinetics assumed responsibility for the costs and activities
associated with the continued development of ispinesib and SB-743921,
subject to GSK's option to resume responsibility for some or all
development and commercialization activities associated with each of these
novel drug candidates. The November 2006 amendment superseded a September
2005 amendment to the collaboration and license agreement, which
specifically related to SB-743921.
About Cytokinetics
Cytokinetics is a biopharmaceutical company focused on the discovery,
development and commercialization of novel small molecule drugs that may
address areas of significant unmet clinical needs. Cytokinetics'
development efforts are directed to advancing multiple drug candidates
through clinical trials to demonstrate proof-of-concept in humans,
specifically in the areas of heart failure and cancer. Cytokinetics'
cardiovascular disease program is focused to cardiac myosin, a motor
protein essential to cardiac muscle contraction. Cytokinetics' lead
compound from this program, CK-1827452, a novel small molecule cardiac
myosin activator, recently entered Phase II clinical trials for the
treatment of heart failure in 2007. Under a strategic alliance established
in 2006, Cytokinetics and Amgen Inc. plan to conduct research with
activators of cardiac myosin in order to identify potential treatments for
patients with heart failure. Amgen has obtained an option for the joint
development and commercialization of CK-1827452 exercisable during a
defined period, the ending of which is dependent on Cytokinetics' conduct
of further clinical trials of CK-1827452. Cytokinetics' cancer program is
focused on mitotic kinesins, a family of motor proteins essential to cell
division. Cytokinetics is developing two novel drug candidates that have
arisen from this program, ispinesib and SB-743921, each a novel inhibitor
of kinesin spindle protein (KSP), a mitotic kinesin. Ispinesib has been
the subject of a broad clinical trials program comprised of nine Phase II
clinical trials as well as eight Phase I or Ib clinical trials.
Cytokinetics plans to conduct additional clinical trials with ispinesib and
is conducting a Phase I/II trial of SB-743921 in non-Hodgkin's lymphoma.
Under a strategic alliance established in 2001, Cytokinetics and
GlaxoSmithKline (GSK) are conducting research and development activities
focused on the potential treatment of cancer. GSK has obtained an option
for the joint development and commercialization of ispinesib and SB-743921,
exercisable during a defined period. Cytokinetics and GSK are conducting
collaborative research activities directed to the mitotic kinesin
centromere-associated protein E (CENP-E). GSK-923295, a CENP-E inhibitor,
is being developed under the strategic alliance by GSK. GSK began a Phase I
clinical trial with GSK-923295 in 2007. All of these drug candidates have
arisen from Cytokinetics' research efforts and are directed towards the
cytoskeleton. The cytoskeleton is a complex biological infrastructure
that plays a fundamental role within every human cell. Cytokinetics' focus
on the cytoskeleton enables it to develop novel and potentially safer and
more effective classes of drugs directed at treatments for cancer and
cardiovascular disease. Additional information about Cytokinetics can be
obtained at www.cytokinetics.com.
This press release contains forward-looking statements for purposes of the
Private Securities Litigation Reform Act of 1995 (the "Act"). Cytokinetics
disclaims any intent or obligation to update these forward-looking
statements, and claims the protection of the Safe Harbor for
forward-looking statements contained in the Act. Examples of such
statements include, but are not limited to, statements relating to the
expected initiation and scope of Cytokinetics' and its partners' research
and development programs, including statements regarding initiation of
clinical trials; the potential benefits of Cytokinetics' drug candidates
and potential drug candidates, including the benefits of mitotic kinesin
inhibitors; and the enabling capabilities of Cytokinetics' biological
focus. Such statements are based on management's current expectations, but
actual results may differ materially due to various risks and
uncertainties, including, but not limited to, potential decisions by GSK to
postpone or discontinue development efforts for GSK-923295; potential
difficulties or delays in the development, testing, regulatory approval,
production and marketing of Cytokinetics' drug candidates that could slow
or prevent clinical development, product approval or market acceptance,
including risks that current and past results of clinical trials or
preclinical studies may not be indicative of future clinical trials
results, patient enrollment for clinical trials may be difficult or
delayed, Cytokinetics' drug candidates may have unexpected adverse side
effects or inadequate therapeutic efficacy, and Cytokinetics may be unable
to obtain and maintain patent or trade secret protection for its
intellectual property; Cytokinetics may incur unanticipated research and
development and other costs or be unable to obtain additional financing if
necessary; standards of care may change or others may introduce products or
alternative therapies for the treatment of indications Cytokinetics' drug
candidates and potential drug candidates currently or potentially target;
and risks and uncertainties relating to the timing and receipt of funds
under Cytokinetics' collaborations. For further information regarding these
and other risks related to Cytokinetics' business, investors should consult
Cytokinetics' filings with the Securities and Exchange Commission.
Contacts:
Scott R. Jordan (Media)
Director, Corporate Development
(650) 624-3000
Christopher S. Keenan (Investors)
Director, Investor Relations
(650) 624-3000
