Cytokinetics, Incorporated (Nasdaq: CYTK) today announced the initiation of
a Phase I/II clinical trial of its second Kinesin Spindle Protein (KSP)
inhibitor, SB-743921, in patients with non-Hodgkin's lymphoma (NHL).
Cytokinetics is conducting this clinical trial in order to expand the
development activities for SB-743921, based on a recently amended agreement
with GlaxoSmithKline (GSK). SB-743921 is the second drug candidate in
clinical development arising from a strategic collaboration between
Cytokinetics and GSK to discover, develop and commercialize novel small
molecule therapeutics targeting human mitotic kinesins for applications in
the treatment of cancer and other diseases. GSK is conducting a broad Phase
II clinical trials program for the lead drug candidate from this program,
the KSP inhibitor ispinesib (SB-715992), and is evaluating SB-743921 in an
ongoing Phase I trial in patients with advanced solid tumors.
This Phase I/II clinical trial is an open-label, non-randomized study
to investigate the safety, tolerability, pharmacokinetic, and
pharmacodynamic profile of SB-743921, administered as a one-hour infusion
on days 1 and 15 of a 28 day schedule, in patients with non-Hodgkin's
lymphoma. The objective of the Phase I portion of the clinical trial is to
identify the maximum tolerated dose (MTD) of SB-743921 on this schedule, in
patients with either Hodgkin's or non-Hodgkin's lymphoma, first without
prophylactic administration of granulocyte colony stimulating factor
(GCSF). If the dose-limiting toxicity determining this first MTD is
neutropenia, a second MTD will be determined with SB-743921 given with
prophylactic administration of GCSF. Following review of the Phase I data
from this clinical trial, the optimal dose and regimen of SB-743921 (i.e.,
without or with prophylactic administration of GCSF) will be determined for
Phase II. In Phase II, 70 NHL patients, with either aggressive or indolent
disease, are planned to be treated with the objective of evaluating
frequency and duration of disease response in these patients.
"We are excited about the initiation of this clinical trial in patients
with non-Hodgkin's lymphoma," stated Dr. Andrew A. Wolff, Cytokinetics'
Senior Vice President of Clinical Research and Development and Chief
Medical Officer. "The advancement of SB-743921 into this additional Phase
I/II clinical trial represents a significant step forward and is consistent
with the vision of our alliance with GSK to broadly explore the role of
inhibitors of KSP such as SB-743921."
About SB-743921
In September of 2005, Cytokinetics and GSK announced an amendment to
their original agreement to support further expansion of the development
activities for SB-743921. Under the terms of the amendment, Cytokinetics is
responsible for leading and funding development activities to explore the
potential application of SB-743921 for the treatment of non-Hodgkin's
lymphoma, Hodgkin's lymphoma and multiple myeloma, subject to the option
for GSK to resume responsibility for development and commercialization
activities for SB-743921 for these indications during a defined period.
Cytokinetics' development activities will be conducted in parallel with
GSK's conduct of development activities for SB-743921 in other indications
and for ispinesib.
In May of 2005, Cytokinetics and GSK presented interim data from an
ongoing open-label, non-randomized, dose-finding Phase I clinical trial in
patients with advanced solid tumors at the American Society of Clinical
Oncologists (ASCO) annual meeting. Based on the interim analysis, it was
determined that SB-743921 appeared to have an acceptable tolerability
profile on a once every 21 day schedule. The dose-limiting toxicities
reported at that time were prolonged neutropenia, febrile neutropenia (with
or without infection), elevated transaminases, hyperbilirubinemia and
hyponatremia. Neurotoxicities, mucositis, thrombocytopenia, alopecia and
nausea/vomiting requiring pre-medication had not been observed. That trial
is still ongoing at this time. SB-743921 is structurally distinct from
ispinesib, Cytokinetics' most advanced drug candidate under the strategic
alliance with GSK.
Background on Cytokinetics and GlaxoSmithKline Strategic Alliance
In June 2001, Cytokinetics and GSK announced that the two companies had
entered into a broad strategic collaboration to discover, develop and
commercialize novel small molecule therapeutics targeting mitotic kinesins
for applications in the treatment of cancer and other diseases. Under the
original terms of the agreement, GSK committed funding of approximately $50
million over the minimum 5-year research term, including a $14 million
upfront cash payment and a $14 million purchase of Cytokinetics preferred
stock. In addition, GSK could make milestone payments to Cytokinetics of up
to an aggregate of $30-50 million per target for products directed to each
mitotic kinesin target. GSK is responsible for worldwide development and
commercialization of products arising from the collaboration. Cytokinetics
will receive royalties from the sale of any resulting products. In
addition, Cytokinetics retains a product-by-product option to co-fund
certain development activities, thereby increasing its royalty and
affording co-promotion rights in North America. During the collaboration,
targets may revert to Cytokinetics for independent research and
development, with GSK retaining an option to resume joint activities. In
September 2005, Cytokinetics and GSK announced an amendment to their
original agreement to support further expansion of the development
activities for SB-743921. Based on Cytokinetics' expanded role under the
amendment in the development of SB-743921, Cytokinetics may receive
additional pre-commercialization payments from GSK based on the achievement
of certain milestones for SB-743921 for the additional indications
described above and increased royalties from GSK on net sales of products
containing SB-743921 under certain scenarios.
About Ispinesib
Ispinesib is a novel small molecule inhibitor of Kinesin Spindle
Protein (KSP), a mitotic kinesin protein essential for proper cell
division. Ispinesib is the first drug candidate in clinical development
that has arisen from a broad strategic collaboration between Cytokinetics
and GlaxoSmithKline (GSK) to discover, develop and commercialize novel
small molecule therapeutics targeting human mitotic kinesins for
applications in the treatment of cancer and other diseases. GSK is
conducting a broad clinical trials program for ispinesib designed to study
the drug candidate in multiple tumor types, combination regimens and dosing
schedules. GSK is currently evaluating ispinesib in two Phase II clinical
trials being conducted in patients with each of ovarian and breast cancers
and two Phase Ib clinical trials designed to evaluate ispinesib in
combination with each of carboplatin and capecitabine. Interim data from
the ongoing breast cancer clinical trial and data from the
platinum-refractory and the platinum-sensitive treatment arms of the
non-small cell lung cancer clinical trial were announced recently. Interim
data from the ongoing breast cancer trial were presented in December 2005
at the San Antonio Breast Cancer Symposium in San Antonio, Texas. In this
Phase II clinical trial enrolling patients with advanced breast cancer, the
best overall responses observed with ispinesib administered as monotherapy
have been partial responses in three of thirty-three evaluable patients to
date. In the platinum-refractory treatment arm of a Phase II clinical trial
enrolling patients with non-small cell lung cancer, the best overall
response observed with ispinesib administered as monotherapy has been
disease stabilization in 25% of evaluable patients (N=20) with a median
time to progression (TTP) of 12 weeks (overall median TTP was six weeks).
In the platinum-sensitive treatment arm of this Phase II clinical trial,
the best overall response observed with ispinesib administered as
monotherapy has been disease stabilization in 50% of evaluable patients
(N=20) with a median time to progression (TTP) of 17 weeks (overall median
TTP was six weeks). In addition to the ongoing studies being conducted by
GSK, the National Cancer Institute (NCI) continues five other Phase II
clinical trials evaluating ispinesib in other tumor types, including
melanoma, head and neck, hepatocellular, colorectal and prostate cancers.
In addition, the NCI plans to conduct one additional Phase II clinical
trial in patients with renal cell carcinoma. The NCI is also conducting two
other Phase I clinical trials evaluating an alternative schedule of
ispinesib in leukemia and advanced solid tumors.
About Cytokinetics
Cytokinetics is a leading biopharmaceutical company focused on the
discovery, development and commercialization of novel small molecule drugs
that specifically target 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, cardiovascular disease and other diseases.
Cytokinetics has developed a cell biology driven approach and proprietary
technologies to evaluate the function of many interacting proteins in the
complex environment of the intact human cell. Cytokinetics employs the
PUMA(TM) system and Cytometrix(TM) technologies to enable early
identification and automated prioritization of compounds that are highly
selective for their intended protein targets without other cellular
effects, and may therefore be less likely to give rise to clinical side
effects. Cytokinetics and GlaxoSmithKline (GSK) have entered into a
strategic alliance to discover, develop and commercialize small molecule
therapeutics targeting human mitotic kinesins for applications in the
treatment of cancer and other diseases. Ispinesib, SB-743921 and GSK-923295
are being developed under the strategic alliance with GSK. GSK is
conducting Phase II and Ib clinical trials for ispinesib (SB-715992) and
GSK and Cytokinetics are each conducting a Phase I clinical trial for
SB-743921. Cytokinetics' unpartnered heart failure program is the second
program to leverage the company's expertise in cytoskeletal pharmacology.
Cytokinetics is conducting a Phase I clinical trial with CK- 1827452, a
novel small molecule cardiac myosin activator, for the intravenous
treatment of heart failure and also selected CK-1827452 as a potential drug
candidate for the treatment of chronic heart failure via oral
administration. Additional information about Cytokinetics can be obtained
at:
cytokinetics.
This press release contains forward-looking statements for purposes of
the Private Securities Litigation Reform Act of 1995 and it is the
Company's intent that such statements be protected by the safe harbor
created thereby. Examples of such statements include, but are not limited
to, statements relating to the future initiation and expected focus of
clinical trials by the National Cancer Institute, statements relating to
the potential clinical trials under the amendment of our strategic
collaboration with GlaxoSmithKline, and statements relating to the
potential benefits of the Company's drug candidate and potential drug
candidates and of our proprietary technologies. Such statements are based
on management's current expectations, but actual results may differ
materially due to various factors. Such statements involve risks and
uncertainties, including, but not limited to, those risks and uncertainties
relating to difficulties or delays in development, testing, regulatory
approval, production and marketing of the Company's drug candidates that
could slow or prevent product approval or market acceptance (including the
risk that uncertainty of patent protection for the Company's intellectual
property or trade secrets, the Company's ability to obtain additional
financing if necessary and unanticipated research and development and other
costs). For further information regarding these and other risks related to
the Company's business, investors should consult the Company's filings with
the Securities and Exchange Commission. Cytokinetics does not undertake any
obligation to update forward-looking statements.
Cytokinetics, Incorporated
cytokinetics