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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): June 7, 2006 (June 5, 2006)
CYTOKINETICS, INCORPORATED
(Exact name of registrant as specified in its charter)
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DELAWARE
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000-50633
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94-3291317 |
(State or other jurisdiction
of incorporation)
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(Commission File Number)
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(IRS Employer
Identification No.) |
280 East Grand Avenue
South San Francisco, California 94080
(Address of principal executive offices, including zip code)
650-624-3000
(Registrants telephone number, including area code)
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the
filing obligation of the registrant under any of the following provisions (see General Instruction
A.2. below):
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR
240.14d-2(b)) |
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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR
240.13e-4(c)) |
TABLE OF CONTENTS
ITEM 8.01. OTHER EVENTS.
On June 5, 2006, Cytokinetics, Incorporated issued a press release announcing the presentation
of clinical trials data for its drug candidates ispinesib (SB-715992) and SB-743921 at the 2006
Annual Meeting of the American Society of Clinical Oncology. These clinical trials are being
conducted by Cytokinetics strategic alliance partner
GlaxoSmithKline and the National Cancer
Institute. A copy of this press release is being filed with this Current Report on Form 8-K, is
attached hereto as Exhibit 99.1, and is hereby incorporated by reference into this Item 8.01.
ITEM 9.01. FINANCIAL STATEMENTS AND EXHIBITS.
(c) Exhibits.
The following Exhibit is filed as part of this Current Report on Form 8-K:
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Exhibit No. |
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Description |
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99.1
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Press Release, dated June 5, 2006. |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly
caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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CYTOKINETICS, INCORPORATED
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By: |
/s/
Sharon Surrey-Barbari |
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Sharon Surrey-Barbari |
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Senior Vice President, Finance and Chief Financial Officer |
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Date: June 7, 2006
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EXHIBIT INDEX
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Exhibit No. |
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Description |
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99.1
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Press Release, dated June 5, 2006. |
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exv99w1
Exhibit 99.1
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Contacts: |
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Cytokinetics, Incorporated
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Burns McClellan, Inc. |
Sharon Surrey-Barbari
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Clay A. Kramer (investors) |
SVP, Finance & CFO
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Justin Jackson (media) |
(650) 624-3000
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(212) 213-0006 |
CYTOKINETICS ANNOUNCES THE PRESENTATION OF CLINICAL TRIALS DATA
AT THE 2006 ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
South San Francisco, CA., June 5, 2006 Cytokinetics, Incorporated (Nasdaq: CYTK) announced today
that data for ispinesib (SB-715992) and SB-743921, from clinical trials being conducted by
GlaxoSmithKline (GSK) or the National Cancer Institute (NCI), were presented in oral and poster
sessions at the 2006 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta,
Georgia. The presentations related to four clinical trials, a Phase II clinical trial evaluating
ispinesib in patients with metastatic colorectal cancer, a Phase Ib clinical trial evaluating
ispinesib in combination with carboplatin, a Phase Ib clinical trial evaluating a new dosing
schedule for ispinesib and a Phase I clinical trial for SB-743921.
Ispinesib and SB-743921 are both novel, chemically-distinct, small molecule inhibitors of kinesin
spindle protein (KSP), a mitotic kinesin essential for proper cell division. Both drug candidates
have arisen from a broad 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.
Ispinesib
The poster entitled, A Randomized Phase II Non-Comparative Study of Ispinesib Given Weekly or
Every Three Weeks in Metastatic Colorectal Cancer: A California Cancer Consortium Study (CCC-P),
was presented by A.B. El-Khoueiry, University of Southern California/Norris Comprehensive Cancer
Center, Los Angeles, CA, on June 3, 2006. The primary objective of this clinical trial was to
evaluate the response rate of patients with metastatic colorectal cancer treated with ispinesib as
monotherapy. The secondary objectives were to determine time to tumor progression, progression
free survival (PFS), overall survival and toxicity. Patients were randomized to receive ispinesib
7 mg/m2 on Days 1, 8, and 15 of a 28 day schedule (Arm A) or 18 mg/m2 every 21 days (Arm
B). A total of sixty-four patients were enrolled into this trial (33 in Arm A; 31 in Arm B). The
median number of cycles was 2 for each arm. Eight patients had stable disease (3 in Arm A; 5 in Arm
B) and 49 had progressive disease (25 in Arm A; 24 in Arm B). Response data were not available in
7 patients as they went off treatment too early to assess response. PFS was 49 days in Arm A (95%
CI: 44 to 51) and 37 days in Arm B (95% CI: 35 to 42 days). The authors concluded that ispinesib
did not manifest an objective response rate on the two schedules evaluated in heavily pretreated
patients with colorectal cancer. The most common grade 3/4 toxicities in Arm A included
neutropenia (n=3), nausea (n=3), vomiting (n=2) and fatigue (n=2). The most common grade 3/4
toxicity in Arm B was neutropenia (n=20), only one of which was febrile. The authors concluded
that the weekly dose given for 3 weeks every 28 days (Arm A) appeared to have a more favorable
toxicity profile compared to the once every 21 day schedule (Arm B).
The poster entitled, Phase I Study of Ispinesib in Combination with Carboplatin in Patients with
Advanced Solid Tumors, was presented by Suzanne F. Jones, Sarah Cannon Research Institute,
Nashville, TN, on Sunday, June 4, 2006. The primary objectives of this clinical trial were to
evaluate the safety and tolerability of the combination of ispinesib with carboplatin, to determine
the optimally tolerated regimen (OTR) and to characterize the pharmacokinetics profiles of
ispinesib and carboplatin when administered together. In this clinical trial, 28 patients were
enrolled and treated at six dose levels. The OTR was determined to be ispinesib at 18 mg/m2
(the maximum tolerated dose (MTD) for ispinesib when administered as a monotherapy) and
carboplatin at a target AUC of 6 mg/ml min; both administered on a once every 21 days (Q21D)
schedule. Dose limiting toxicities (DLTs) included prolonged (> 5 days) grade 4
neutropenia, grade 4 thrombocytopenia and grade 3 febrile neutropenia. At the OTR, ispinesib
concentrations were not affected by carboplatin. The best response was a partial response (PR) at
cycle 2 in one patient with breast cancer; a total of 13 patients (46%) had a best response of
stable disease (SD) with durations ranging from 3 to 9 months.
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Cytokinetics American Society of Clinical Oncology Press Announcement
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The poster entitled, A Phase I Dose Escalation Trial of Ispinesib (SB-715992) Administered Days
1-3 of a 21-day Cycle in Patients with Advanced Solid Tumors, was presented by Elizabeth I. Heath,
Karmanos Cancer Institute, on Sunday, June 4, 2006. The primary objectives of this clinical trial
were to assess the safety and tolerability of ispinesib and to determine the DLT and MTD at this
dosing regimen. Twenty-seven patients with various tumor types were enrolled. Grade 3 and grade 4
toxicities were noted at 4 mg/m2, including neutropenia and leukopenia. At 6
mg/m2, grade 3 neutropenia was reported and at 8 mg/m2, grade 3 neutropenia
and leukopenia were reported. As a result, 6 mg/m2 was further evaluated as a potential
MTD. In this clinical trial, stable disease was reported in two patients with renal cell carcinoma
and a minor response was noted in one patient with bladder cancer.
SB-743921
The oral presentation entitled Phase I Study to Determine Tolerability and Pharmacokinetics (PK)
of SB-743921, a Novel Kinesin Spindle Protein (KSP) Inhibitor was presented by Dr. Kyle Holen,
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin on June 3, 2006. The
primary objectives of this clinical trial were to determine the DLTs and to establish the MTD of
SB-743921 administered intravenously on a Q21D schedule; secondary objectives included assessment
of the safety and tolerability of SB-743921, to characterize the pharmacokinetics of SB-743921 on
this schedule and to make a preliminary assessment of the antitumor activity of SB-743921. By
study design, dose escalation continued until dose-limiting toxicities were observed. Forty-four
patients with a variety of solid tumors were enrolled. The recommended phase II dose of SB-743921
on the Q21D schedule is 4 mg/m2, although dosing did reach 8 mg/m2. The
observed toxicities at the recommended Phase II dose were manageable. DLTs in this clinical trial
consisted predominantly of neutropenia and elevations in hepatic enzymes and bilirubin. Neutropenia
nadir was day 6-8 with recovery by day 15. The median half-life of SB-743921 was 29 hours.
Disease stabilization (range 9-45 weeks) was observed in 7 patients. A patient with
cholangiocarcinoma had a confirmed PR at the MTD at cycle 10.
These presentations further the clinical understanding of KSP inhibitors for the treatment of
cancer, stated Dr. James Sabry, Cytokinetics Chief Executive Officer. These data are consistent
with previously reported data which underscores the potential combinability of ispinesib with
currently used chemotherapeutics. We are encouraged by the clinical activity as measured by tumor
shrinkage in each of the Phase Ib combination trial with ispinesib and carboplatin and the Phase I
trial of SB-743921 in cholangiocarcinoma. These results add to the growing clinical experience
with KSP inhibitors and may be helpful in designing other Phase II and Phase III clinical trials.
Background on KSP 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 the
peripheral nervous system. Neuropathies 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.
The strategic alliance between Cytokinetics and GSK has yielded two novel drug candidates,
ispinesib (SB-715992) and SB-743921. Ispinesib and SB-743921 are structurally distinct small
molecule compounds that modulate cell proliferation and promote cancer cell death by specifically
inhibiting kinesin spindle protein (KSP). KSP is a mitotic kinesin that is essential for cell
proliferation, a process which when unregulated, results in tumor growth. Mitotic kinesins are
essential to mitosis, and, unlike tubulin, appear to have no role in unrelated cellular functions.
We believe that drugs that inhibit KSP 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, avoiding many of the toxicities commonly experienced by
patients treated with existing anti-mitotic drugs.
Cytokinetics American Society of Clinical Oncology Press Announcement
Page 3
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 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 this 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.
In addition to the ongoing studies being conducted by GSK, the National Cancer Institute (NCI) is
five other Phase II clinical trials evaluating ispinesib in other tumor types, including melanoma,
head and neck, hepatocellular, colorectal and prostate cancers and melanoma. In addition, the NCI
plans to conduct an additional Phase II clinical trial in patients with renal cell carcinoma. The
NCI is also conducting two other Phase I clinical trials evaluating a new schedule of ispinesib,
one in leukemia and another in advanced solid tumors.
About SB-743921
SB-743921, Cytokinetics second KSP inhibitor to enter clinical trials under the strategic alliance
with GSK, is structurally distinct from ispinesib, Cytokinetics most advanced drug candidate. In
September 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-Hodgkins lymphoma (NHL), Hodgkins disease and
multiple myeloma, subject to GSKs option 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 GSKs development
activities for SB-743921 in other indications and for ispinesib. In April 2006, Cytokinetics
announced the initiation of a Phase I/II clinical trial of SB-743921 in patients with NHL, in
connection with an expanded development program for SB-743921. 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, and to assess the potential efficacy of the maximum tolerated dose of SB-743921
administered on this schedule in patients with NHL.
About Cytokinetics
Cytokinetics is a 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 its PUMA system and Cytometrix 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 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-715992), 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, a Phase I clinical trial for SB-743921, and Cytokinetics
is conducting a Phase I/II trial of SB-743921 in NHL. Cytokinetics unpartnered cardiovascular
disease program is the second program to leverage the companys expertise in cytoskeletal
pharmacology. Cytokinetics is conducting a Phase I clinical trial with intravenous CK-1827452, a
novel small molecule cardiac myosin activator, for the intravenous treatment of heart failure and
also has 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
http://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 about our partners planned clinical research and development activities and
statements regarding the potential benefits of our drug candidates and potential drug candidates,
the enabling capabilities of our proprietary technologies and the benefits of data obtained from
completed clinical trials. Such statements are based on managements current expectations, but
actual results may differ materially due to various factors. Such statements involve
Cytokinetics American Society of Clinical Oncology Press Announcement
Page 4
risks and uncertainties, including, but not limited to, those risks and uncertainties relating
to decisions by the NCI to postpone or discontinue development efforts for one or more
compounds, difficulties or delays in patient enrollment for clinical trials, unexpected adverse
side effects or inadequate therapeutic efficacy of our drug candidates and other potential
difficulties or delays in development, testing, regulatory approval, production and marketing of
Cytokinetics drug candidates that could slow or prevent clinical development, product approval or
market acceptance (including the risks relating to uncertainty of patent protection for
Cytokinetics intellectual property or trade secrets,Cytokinetics ability to obtain additional
financing if necessary and unanticipated research and development and other costs), the conduct of
activities and continued funding under Cytokinetics collaborations and the implementation and
maintenance of procedures, policies, resources and infrastructure relating to compliance with new
or changing laws, regulations and practices. For further information regarding these and other
risks related to Cytokinetics business, investors should consult Cytokinetics filings with the
Securities and Exchange Commission.
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