Cytokinetics Announces Interim Clinical Trial Data Relating to Ispinesib Presented at the 2008 ASCO Breast Cancer

Mon Sep 8, 2008 7:30am EDT

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Cytokinetics, Incorporated (NASDAQ: CYTK) announced that data from its
ongoing Phase I/II clinical trial of ispinesib were presented in a poster
at the 2008 American Society of Clinical Oncology (ASCO) Breast Cancer
Symposium held on September 5-7, 2008 in Washington, DC.

    A poster entitled, "A Phase I-II Trial of Ispinesib, a Kinesin Spindle
Protein (KSP) Inhibitor, Dosed Every Two Weeks in Patients (pts) with
Locally Advanced (LA) or Metastatic Breast Cancer (MBC) Previously
Untreated with Chemotherapy (CT) for Metastatic Disease or Recurrence,"
was presented by Henry Gomez, MD, Attending Physician and Chief of Medical
Oncology, Departamento de Investigacion, Instituto Nacional de
Enfermedades Neoplasicas (INEN) in Lima, Peru on September 5, 2008. The
primary objectives of the Phase I portion of this clinical trial are to
determine the dose limiting toxicities (DLTs) and maximum tolerated dose
and to assess the safety and tolerability of ispinesib administered as a
1-hour intravenous infusion on days 1 and 15 of a 28-day cycle. The
secondary objectives are to characterize the pharmacokinetics of
ispinesib on this schedule and to evaluate the effect of ispinesib on
biomarkers of cell proliferation in patients with accessible tumors.

    Interim results were provided for 15 patients who had been enrolled at one
of three dose levels of ispinesib (10 mg/m2, 12 mg/m2 and 14 mg/m2) and
had completed at least one cycle of treatment. At the time of data
analysis, thirteen patients were evaluable for safety and efficacy. Tumor
response was assessed for an additional two patients subsequently treated
at 12 mg/m2. Two of 7 patients treated at the 14 mg/m2 dose level had
protocol-defined DLTs of transient Grade 3 increases in the liver enzymes
ALT and AST following cycle 1, day 15 dosing. As a result of these DLTs at
14 mg/m2, the 12 mg/m2 cohort was expanded to 6 patients, and no DLTs were
observed at the latter dose level. Because the 12 mg/m2 dose level was
thus demonstrated to be tolerable, and because the authors concluded that
the DLTs of Grade 3 ALT/AST increases at 14 mg/m2 dose level had a
questionable temporal relationship to the administration of ispinesib,
plans are underway to further evaluate the 14 mg/m2 dose level. The most
frequent adverse event was neutropenia, reported in 85% of patients, with
69% of patients experiencing Grade 3 or 4 neutropenia. Other than
neutropenia and the Grade 3 ALT/AST increases described above, there were
no other Grade 3 or 4 adverse events; no alopecia or neurotoxicity was

    The best responses observed to date in the Phase I portion of this ongoing
Phase I/II clinical trial were investigator-reported reductions of 30% or
greater in the sum of the target lesion diameters, reported in 3 patients.
One of these patients had an investigator-reported partial response
according to the Response Evaluation Criteria in Solid Tumors (RECIST).
Three patients had investigator-reported stable disease of 4 months or
longer according to RECIST.

    "These data are encouraging and support the ongoing development of this
novel mechanism anti-mitotic chemotherapeutic," stated Dr. Gomez.
"Ispinesib has been well-characterized in prior studies and has shown a
favorable tolerability profile. These data support the safety and
tolerability of this drug candidate on a more dose-dense schedule and
suggest the potential for amplified clinical activity."

    "We are pleased with the progress of this clinical trial evaluating
ispinesib monotherapy in chemotherapy-naive women with locally advanced or
metastatic breast cancer," stated Dr. Andrew A. Wolff, Cytokinetics'
Senior Vice President of Clinical Research and Development and Chief
Medical Officer. "We look forward to sharing more data with the medical
community as this trial continues."

    Ispinesib in Breast Cancer

    In June 2008, as part of a poster session at the ASCO Annual Meeting,
Cytokinetics announced interim data from the Phase I portion of this
ongoing Phase I/II clinical trial. At that time, the authors concluded
that preliminary data suggest that ispinesib is well-tolerated when dosed
on days 1 and 15 every 28 days at doses up to 12 mg/m2.

    In June 2007, Cytokinetics reported final results of a Phase II clinical
trial conducted by GlaxoSmithKline (GSK) designed to evaluate the safety
and efficacy of ispinesib in the second- or third-line treatment of
patients with locally advanced or metastatic breast cancer whose disease
had recurred or progressed despite treatment with anthracyclines and
taxanes. In that trial, patients received ispinesib as monotherapy at 18
mg/m2 as a 1-hour intravenous infusion every 21 days. The primary endpoint
of the trial was objective response by RECIST. Partial responses, observed
in 4 of 45 evaluable patients, were confirmed by independent radiology
review and were seen in liver, lung and lymph node metastases. The
duration of these responses, also independently reviewed, ranged from 7.1
weeks to 30.0 weeks. The median time to progression in the treated
population was 5.9 weeks. The adverse events were manageable, predictable
and consistent with those seen in the Phase I trials of ispinesib. The
most common grade 3/4 adverse events observed in the 50 patients
evaluable for safety were neutropenia (21 patients), febrile neutropenia
(4 patients) and neutropenic sepsis (1 patient).

    Clinical Trials of Ispinesib

    Ispinesib has been the subject of a broad Phase II clinical trials program
under the sponsorship of GSK and of the National Cancer Institute (NCI).
GSK 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, Cytokinetics believes clinical activity with ispinesib has been
observed in breast, ovarian and non-small cell lung cancer, with the most
robust clinical activity observed in GSK's Phase II clinical trial
evaluating ispinesib in the treatment of patients with locally advanced
or metastatic breast cancer that failed to respond or recurred after
treatment with taxanes and anthracyclines.

    In addition, GSK sponsored three dose-escalating Phase Ib clinical trials.
Each of these 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 Phase Ib clinical trials of ispinesib in combination with
carboplatin and docetaxel were completed in 2006 and demonstrated that
ispinesib has an acceptable tolerability profile in combination with
these standard chemotherapeutic agents. The results of the Phase Ib
clinical trial evaluating ispinesib in combination with capecitabine were
announced in June 2008. The combination of ispinesib with capecitabine
was found to have had an acceptable tolerability profile on the 21-day
schedule investigated in the trial. The dose limiting toxicity in this
combination regimen was consistent with the monotherapy toxicities of
ispinesib (prolonged neutropenia) and capecitabine (rash). In this
combination trial, the best response observed by RECIST was a partial
response in a patient with advanced breast cancer and 11 patients had a
response of stable disease.

    Cytokinetics is conducting, at its expense, a focused development program
for ispinesib in breast cancer specifically designed to supplement the
Phase I and Phase II clinical trials sponsored by GSK that demonstrated
clinical activity in the treatment of patients with metastatic breast
cancer and an acceptable tolerability profile for ispinesib in combination
with capecitabine. The Phase I/II clinical trial from which interim
results were announced today is an integral part of this development
program, the objective of which is to evaluate the possibility that
ispinesib administered as monotherapy on days 1 and 15 of a 28-day cycle
may demonstrate an amplified signal of clinical activity in
chemotherapy-naive breast cancer patients.

    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, both inhibitors of KSP,
and GSK-923295, an inhibitor of centromere-associated protein E (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, exercisable during a defined period. GSK-923295,
now in a Phase I clinical trial in advanced cancers, is being developed
under the strategic alliance by GSK. In June 2008, 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. Cytokinetics will receive
royalties from the sale of any products arising from the strategic
alliance that GSK progresses to commercialization. For products that GSK
progresses in development, Cytokinetics retains a product-by-product
option to co-fund certain later-stage development activities, thereby
providing Cytokinetics an opportunity to increase its potential royalties
and obtain co-promotion rights in North America.

    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'
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, entered Phase II clinical trials for the treatment of
heart failure in 2007. Under a strategic alliance established in 2006,
Cytokinetics and Amgen Inc. are performing joint research focused on
identifying and characterizing activators of cardiac myosin as back-up and
follow-on potential drug candidates to CK-1827452. Amgen has obtained an
option for an exclusive license to develop and commercialize CK-1827452,
subject to Cytokinetics' development and commercial participation rights.
Cytokinetics' cancer program is focused on mitotic kinesins, a family of
motor proteins essential to cell division. Under a strategic alliance
established in 2001, Cytokinetics and GlaxoSmithKline (GSK) are conducting
research and development activities focused on the potential treatment of
cancer. 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. Cytokinetics is
sponsoring a Phase I/II clinical trial of ispinesib as monotherapy as a
first-line treatment in chemotherapy-naive patients with locally advanced
or metastatic breast cancer. In addition, Cytokinetics is conducting a
Phase I/II trial of SB-743921 in patients with non-Hodgkin or Hodgkin
lymphoma. GSK has obtained an option for the joint development and
commercialization of ispinesib and SB-743921. 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. In April 2008,
Cytokinetics announced the selection of a potential drug candidate
directed towards skeletal muscle contractility which may be developed as
a potential treatment for skeletal muscle weakness associated with
neuromuscular diseases or other conditions. All of these drug candidates
and potential 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. Additional information about Cytokinetics can be
obtained at

    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
Cytokinetics' research and development programs, including the design,
conduct and results of clinical trials and the availability of clinical
trial results; the properties and potential benefits of Cytokinetics' drug
candidates and potential drug candidates; and Cytokinetics' potential
receipt of funds and anticipated role in development and commercialization
activities under its collaboration and license agreement with GSK. 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 difficulties or delays in the
development, testing, regulatory approval or production of Cytokinetics'
drug candidates that could slow or prevent clinical development or product
approval, 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 or conduct of clinical trials may be
difficult or delayed, Cytokinetics' drug candidates may have adverse side
effects or inadequate therapeutic efficacy, the U.S. Food and Drug
Administration or foreign regulatory agencies may delay or limit
Cytokinetics' or its partners' ability to conduct clinical trials, and
Cytokinetics may be unable to obtain or maintain patent or trade secret
protection for its intellectual property; GSK may decide to postpone or
discontinue development activities for GSK-923295; Cytokinetics may incur
unanticipated research and development and other costs or be unable to
obtain additional financing necessary to conduct development of its
products; standards of care may change and others may introduce products
or alternative therapies for the treatment of indications Cytokinetics'
drug candidates and potential drug candidates may target; and risks and
uncertainties relating to the timing and receipt of payments from
Cytokinetics' partners, including milestones and royalties on future
potential product sales under its collaboration agreements with such
partners. For further information regarding these and other risks related
to Cytokinetics' business, investors should consult Cytokinetics' filings
with the Securities and Exchange Commission.


Scott R. Jordan (Media)
Director, Corporate Development
(650) 624-3000

Christopher S. Keenan (Investors)
Director, Investor Relations
(650) 624-3000

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