Richard Davies wrote: The UK has a good crop of technology pioneers in cloud computing - for example ElasticHosts, FlexiScale, Flexiant, OnApp - and also some strong government initiatives such as G-Cloud.
We will have to see whether this kind of technical leadership converts into swift mass-market adoption or not.
SOUTH SAN FRANCISCO, CA -- (MARKET WIRE) -- 04/18/07 -- Cytokinetics, Incorporated (NASDAQ: CYTK) announced the presentation of non-clinical data at the 2007 Annual
Meeting of the American Association for Cancer Research (AACR) held in Los
Angeles, CA from April 14-18, 2007. The presentations covered data
evaluating ispinesib, a novel inhibitor of kinesin spindle protein (KSP),
in models of multiple myeloma, data evaluating GSK-923295, a novel
inhibitor of centrosome associated protein E (CENP-E) in both biochemical
assays and in xenograft models and data from a separate, novel Cytokinetics
cell-based drug discovery program.
"These presentations demonstrate the advancement of additional research
oncology programs towards further development," stated David J. Morgans,
Jr., Ph.D., Senior Vice President, Preclinical Research and Development.
"This research not only identifies another potential development path for
our leading oncology compound, ispinesib, and underscores enthusiasm for
our potential drug candidate GSK-923295, expected to enter human clinical
trials in 2007, but also points to future development opportunities that
may arise from other ongoing drug discovery activities directed to cell
cycle inhibition."
Ispinesib
The poster presentation entitled, "Kinesin Spindle Protein Inhibition for
the Treatment of Multiple Myeloma," contained data arising from
non-clinical studies designed to examine whether spindle disruption by
inhibition of KSP with ispinesib may have therapeutic potential in the
treatment of multiple myeloma. This presentation demonstrated that KSP
inhibition with ispinesib was able to induce growth arrest and apoptosis in
myeloma cells, and overcome resistance to both conventional drugs and novel
agents, such as bortezomib. Moreover, the authors concluded that
preferential activity against transformed plasma cells with sparing of
normal bone marrow cells provides a rationale for translation of ispinesib
into the clinic to combat relapsed/refractory multiple myeloma.
GSK-923295
The poster presentation entitled, "GSK-923295, a Potent and Selective
CENP-E Inhibitor, Has Broad Spectrum Activity Against Human Tumor
Xenografts in Nude Mice," contained data arising from non-clinical research
on GSK-923295. In this presentation, the authors concluded that GSK-923295
is a potent and selective inhibitor of CENP-E. Furthermore, the data
presented support the conclusion that GSK-923295 elicits dose-dependent
increases in mitotic index in Colo205 tumor xenografts and an associated
increase in apoptotic index, which is reflected histologically by an
abundance of apoptotic bodies and mitotic spindles with the majority of
chromosomes aligned at the metaphase plate, and a minority localized near
the spindle poles, a phenotype identical to that which is observed in
vitro. The authors also concluded that GSK-923295 has a broad spectrum of
activity against a range of human tumor xenografts grown in nude mice.
The poster presentation entitled, "Detailed Biochemical Analysis of the
CENP-E Inhibitor GSK-923295," contained data arising from biochemical
analyses of GSK-923295. In this presentation, GSK-923295 was concluded to
be an allostreric and specific inhibitor of human CENP-E and an inhibitor
of the CENP-E microtubule stimulated ATPase. In addition, GSK-923295 was
demonstrated to lock CENP-E onto microtubules and stabilize the ADP-Pi
state of the microtubule-CENP-E complex. The authors concluded that
GSK-923295 has a mode of inhibition consistent with the cellular response,
namely cell cycle arrest with bipolar mitotic spindles and misaligned
chromosomes, and has a unique mechanism of action compared to the KSP
inhibitors, ispinesib and monastrol.
Cytokinetics' Cell-Based Drug Discovery Program
The poster presentation entitled, "Cell-based Discovery and Anti-tumor
Activity of a Novel Mitotic Inhibitor," contained data arising from
Cytokinetics' cell-based oncology drug discovery program. In this
presentation, the authors identified a novel series of tumor-selective,
anti-mitotic compounds which exhibited substantially less interphase
activity than paclitaxel. The data presented demonstrated significant
improvements in potency and drug properties of these compounds that were
achieved without knowledge of the molecular target. Furthermore, the
authors concluded that these compounds induced robust
concentration-dependent cell cycle arrest in mitosis both in vitro and in
vivo and promoted apoptosis.
Clinical Trials for Ispinesib
Ispinesib has been the subject of a broad Phase II clinical trials program
under the sponsorship of GlaxoSmithKline (GSK) and is also being developed
in collaboration with the National Cancer Institute (NCI). Under a
November 2006 amendment to its collaboration and license agreement with
GSK, Cytokinetics has assumed responsibility for the costs and activities
associated with the continued development of the KSP inhibitors, 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. Cytokinetics plans to conduct, at its
expense, a focused development program for ispinesib in breast cancer
specifically designed to supplement the broad series of Phase I and Phase
II clinical trials sponsored by GSK that have demonstrated clinical
activity in the treatment of patients with metastatic breast cancer and
that have shown an acceptable tolerability profile for ispinesib in
combination with standard chemotherapeutics.
GSK has sponsored three Phase II clinical trials, one evaluating ispinesib
as second- or third-line treatment for patients with locally advanced or
metastatic breast cancer, one evaluating ispinesib as second-line treatment
for patients with non-small cell lung cancer and one evaluating ispinesib
as second-line treatment for patients with advanced ovarian cancer.
Enrollment in all of these studies has been closed. To date, clinical
activity for ispinesib has been observed in non-small cell lung cancer and
breast cancer, with the more robust clinical activity observed in a Phase
II clinical trial evaluating ispinesib in the treatment of metastatic
breast cancer patients that have failed treatment with taxanes and
anthracyclines. GSK has informed Cytokinetics that final data is expected
from the breast cancer clinical trial in the first half of 2007 and that a
patient remains on study in the ovarian trial.
In addition, GSK has sponsored three dose-escalating Phase Ib clinical
trials. Each of these clinical trials was designed to evaluate the safety,
tolerability and pharmacokinetics of ispinesib in combination with a
leading anti-cancer therapeutic, one in combination with carboplatin, the
second in combination with capecitabine, and the third in combination with
docetaxel. The clinical trial evaluating ispinesib in combination with
capecitabine is ongoing.
The NCI has sponsored six additional Phase II clinical trials, one
evaluating the potential efficacy of ispinesib in the second-line treatment
of patients with colorectal cancer, one in the first-line treatment of
patients with hepatocellular cancer, one in the first-line treatment of
patients with melanoma, one in the first- or second-line treatment of
patients with head and neck cancers, one in the
second-line treatment of patients with hormone-refractory prostate cancer,
and one in the second-line treatment of patients with renal cell cancer.
Enrollment has been closed for all of these trials; patients remain on
treatment in the renal cell cancer trial. Data are expected from the
hepatocellular cancer, the prostate cancer, the melanoma, and the renal
cell cancer trials in 2007. Data from other clinical trials have already
been reported.
The NCI has completed patient treatment in a Phase I clinical trial
designed to evaluate the safety, tolerability and pharmacokinetics of
ispinesib on an alternative dosing schedule in patients with advanced solid
tumors that have failed to respond to all standard therapies; data from
this trial have already been reported. The NCI is continuing patient
enrollment in a Phase I clinical trial designed to evaluate the safety,
tolerability and pharmacokinetics of ispinesib on an alternative dosing
schedule in patients with acute leukemia, chronic myelogenous leukemia or
advanced myelodysplastic syndromes. Data from this trial are expected in
2007.
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, appear to
have no role in unrelated cellular functions. Cytokinetics believes that
drugs that inhibit KSP and 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.
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, CK-1827452, a novel small molecule cardiac myosin activator,
entered Phase II clinical trials for the treatment of heart failure in
2007. Under a strategic alliance established in 2006, Cytokinetics and
Amgen will 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 to 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 six 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 towards 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 is expected to begin clinical trials with
GSK-923295 in 2007. All of these drug candidates have arisen from
Cytokinetics' research activities 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, timing, conduct, scope and results of Cytokinetics'
and its partners' research and development programs, including initiation
of clinical trials, future presentations concerning Cytokinetics and its
partners' research and development programs, anticipated dates of release
of data from clinical trials; the incremental costs Cytokinetics expects to
incur in connection with its ispinesib development program; and the
potential benefits of Cytokinetics' drug candidates and potential drug
candidates, including the benefits of mitotic kinesin inhibitors; and the
enabling capabilities of our 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, that
GSK or the NCI may decide to postpone or discontinue development efforts
for GSK-923295 or ispinesib, respectively; that there may be difficulties
or delays 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 not be able to obtain and maintain patent or trade secret protection
for its intellectual property; that Cytokinetics may incur unanticipated
research and development and other costs or be unable to obtain additional
financing if necessary; and that standards of care may change or others may
introduce products or alternative therapies for the treatment of
indications which Cytokinetics' drug candidates and potential drug
candidates currently or potentially target. 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