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Exhibit 99.1
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Contacts:
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Cytokinetics, Incorporated
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Burns McClellan, Inc.
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Robert I. Blum
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Clay Kramer (investors)
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President
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Justin Jackson (media)
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(650) 624-3000
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(212) 213-0006
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CYTOKINETICS AND
GLAXOSMITHKLINE AMEND COLLABORATION AND LICENSE
AGREEMENT
Cytokinetics to Assume Clinical Development
Responsibilities for Ispinesib and SB-743921
Company Provides Clinical Update for Phase
II Trial Evaluating Ispinesib in Patients with Breast
Cancer
South San Francisco, CA, November 27, 2006
— Cytokinetics, Incorporated (Nasdaq: CYTK) announced an
amendment of the company’s collaboration and license
agreement with GlaxoSmithKline (GSK), under which Cytokinetics will
assume responsibility for the costs and activities of continued
development of the kinesin spindle protein (KSP) inhibitors
ispinesib (SB-715992) 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.
Under the revised structure, Cytokinetics plans to conduct a
focused development program for ispinesib 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 and
lung cancers and that have shown an acceptable tolerability profile
for ispinesib in combination with standard
chemotherapeutics. Cytokinetics is considering plans to conduct a
focused clinical trials program in breast cancer patients in 2007.
This program would be designed to further define the clinical
activity profile of ispinesib in advanced breast cancer in
preparation for potentially initiating a Phase III clinical trial
of ispinesib for the second-line treatment of advanced
breast cancer . Concurrent with this supplemental program
for ispinesib , the National Cancer Institute (NCI) is
continuing ongoing Phase II and Phase I clinical trials with
ispinesib and Cytokinetics is continuing an ongoing Phase
I/II clinical trial of SB-743921 in non-Hodgkin’s lymphoma
(NHL) that was initiated earlier this year.
"We are pleased to have the opportunity to sponsor additional
activities focused to advancing ispinesib as a potential
next-generation approach for the treatment of breast cancer
alongside our ongoing clinical trial now underway with SB-743921,"
stated James H. Sabry, M.D., Ph.D., Cytokinetics’ Chief
Executive Officer. "We believe that the clinical trials data
generated by GSK, alongside data arising from NCI sponsored trials,
should serve as a foundation for a focused and cost effective
development program going forward."
"We have been engaged with GSK in a collaboration for over five
years. Our research and development collaboration activities have
yielded two novel drug candidates and one potential drug candidate
for the treatment of cancer," stated Andrew A. Wolff, M.D.,
F.A.C.C., Cytokinetics’ Senior Vice President of Clinical
Research and Development and Chief Medical Officer. "We look
forward to reviewing additional clinical trials data for
ispinesib and SB-743921 and are pleased to take a more
prominent role in ongoing development activities."
Update Regarding Phase II Trial Evaluating Ispinesib
in Patients with Breast Cancer
GSK conducted a two-stage Phase II clinical trial 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 this clinical
trial, patients received ispinesib as monotherapy at 18 mg/m
2 as a 1 hour
infusion once every 21 days. As previously announced, in Stage
1 of this clinical trial, the best overall responses observed were
3 partial responses (as measured by the Response Evaluation
Criteria in Solid Tumors, or RECIST) among 33 evaluable patients.
These 3 patients had maximum decreases in tumor size ranging from
46% to 68% with the durations of response ranging from
7.1 weeks to 13.4 weeks. The most common adverse event
was Grade 4 neutropenia. While fully analyzed data from Stage 2 of
this clinical trial have not yet been provided to Cytokinetics, GSK
has recently informed the company that the trial has been closed to
enrollment at 50 patients and that an additional independently
confirmed partial response was observed in the trial.
Moreover, as previously presented at the 18th Annual
EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics in Prague, Czech Republic, a scientific poster
entitled, "Phase I Study of Ispinesib (SB-715992), a Kinesin
Spindle Protein Inhibitor, in Combination with Capecitabine
in Patients with Advanced Solid Tumors," contained data from
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Cytokinetics Collaboration Amendment Announcement
Page 2
an ongoing clinical trial demonstrating that the combination of
ispinesib and capecitabine may have an acceptable
tolerability profile on the clinical trial’s treatment
schedule. The optimally tolerated regimen in this clinical trial
has yet to be defined. However, the maximum tolerated dose of
ispinesib of 18 mg/m 2
, administered as an intravenous infusion every
21 days, was tolerated with therapeutic doses of
capecitabine , specifically daily oral doses of 2000
mg/m 2 and
2500 mg/m 2 for 14 days of a 21 day cycle, and plasma
concentrations of ispinesib were not affected by the
presence of capecitabine . Dose limiting toxicities observed
included Grade 2 rash that did not allow 75% of the
capecitabine doses to be delivered and prolonged Grade 4
neutropenia. In this clinical trial, a total of 12 patients
(including 4 with breast cancer, 3 with colorectal cancer, 3 with
bladder cancer, 1 with thyroid cancer and 1 with tongue cancer) out
of 24 total patients had a best response of stable disease as
defined by the RECIST criteria (median 2.25 months, duration
2-12 months). A patient with breast cancer had the longest
duration of stable disease at 12 months.
Terms of November 2006 Amendment to Collaboration
Agreement
Under the terms of the November 2006 amendment to the
collaboration agreement, Cytokinetics, at its expense, will assume
responsibility for the continued research, development and
commercialization of inhibitors of KSP, including ispinesib
and SB-743921, and other mitotic kinesins, other than
centromere-associated protein E (CENP-E) which is the focus of
translational research activities being conducted by GSK and
Cytokinetics and development activities being conducted by GSK. The
ongoing activities for CENP-E are coordinated under an agreed joint
research program during an extended research term under the
June 2006 amendment to the collaboration agreement. Under the
November 2006 amendment, Cytokinetics’ development of
ispinesib and SB-743921 is subject to GSK’s option to
resume responsibility for the development and commercialization of
either or both drug candidates during a defined period and in
accordance with agreed terms. If GSK exercises its option for a
drug candidate, it will pay Cytokinetics an option fee equal to the
costs Cytokinetics independently incurred for that drug candidate,
plus a premium intended to compensate Cytokinetics for the cost of
capital associated with such costs, subject to an agreed limit for
such costs and premium. Upon GSK exercising its option for a drug
candidate, Cytokinetics may receive additional
pre-commercialization milestone payments with respect to such drug
candidate and increased royalties on net sales of any resulting
product, in each case, beyond those contemplated under the original
agreement. If GSK does not exercise its option for a drug
candidate, Cytokinetics will be obligated to pay royalties to GSK
on the sales of any resulting products. The November 2006
amendment supersedes a previous amendment to the collaboration
agreement dated September 2005, which specifically related to
SB-743921.
Cytokinetics is considering a development plan for the further
evaluation of ispinesib for the treatment of breast cancer
and may further explore the combination treatment approach of
ispinesib
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