Company Provides Update on Cardiovascular and Oncology Clinical Programs
SOUTH SAN FRANCISCO, Calif., Oct. 26 /PRNewswire-FirstCall/ --
Cytokinetics, Incorporated (Nasdaq: CYTK) reported revenues from research
and development collaborations of $0.1 million for the third quarter of
2006. Net loss for the third quarter of 2006 was $14.9 million, or $0.41
per share. As of September 30, 2006, cash, cash equivalents, restricted
cash and marketable securities totaled $93.9 million.
"The third quarter of 2006 was exciting for Cytokinetics as we
presented promising data from our cardiovascular program. We were pleased
that data from our Phase I clinical trial of intravenous CK-1827452 were
warmly received when presented at the Recent and Late Breaking Trials
Session of the 2006 Heart Failure Society of America Meeting in Seattle,"
stated James Sabry, M.D., Ph.D., Cytokinetics' CEO. "In addition, we
initiated an oral bioavailability clinical trial of CK-1827452 in August
that we expect will inform our plans to develop an oral formulation of this
novel drug candidate for the chronic treatment of heart failure. The
possibility of developing both an intravenous and an oral formulation of
CK-1827452 highlights the potential for this drug candidate to treat both
hospitalized patients with acutely decompensated heart failure and
outpatients with chronic heart failure. These activities occurred in
parallel with progress in our ongoing oncology clinical trials programs."
Company Highlights
-- In September, at the Heart Failure Society of America (HFSA)
Meeting, Cytokinetics announced data from a first-in-humans Phase I
clinical trial evaluating intravenous CK-1827452. This clinical
trial was conducted to investigate the safety, tolerability,
pharmacokinetics and pharmacodynamic profile of a six-hour infusion
of CK-1827452 in healthy volunteers. In this Phase I clinical
trial, the maximum tolerated dose (MTD) was determined to be 0.5
mg/kg/hr for the six-hour infusion in healthy volunteers. At this
dose, the six-hour infusion of CK-1827452 produced a mean increase
in left ventricular ejection fraction of 6.8 absolute percentage
points as compared to placebo (p<0.0001). At the same dose, CK-
1827452 also produced a mean increase in fractional shortening of
9.2 absolute percentage points versus placebo (p<0.0001). These
increases in indices of left ventricular function were associated
with an 84 milliseconds mean prolongation of systolic ejection time
(p<0.0001). These mean changes in ejection fraction, fractional
shortening and ejection time were dose-proportional across the range
of doses evaluated in this clinical trial, which were also
characterized by linear, dose-proportional pharmacokinetics. At the
MTD, CK-1827452 was well-tolerated when compared to placebo. The
adverse effects at dose levels exceeding the MTD were associated
with longer prolongations of systolic ejection time and larger
increases in ejection fraction and fractional shortening than those
that were observed with doses at or below the MTD. The
corresponding adverse effects at the higher dose levels in humans
appear similar to the adverse findings observed in the preclinical
safety studies which occurred at similar plasma concentrations.
These effects are believed to be related to an excess of the
intended pharmacologic effect, resulting in excessive prolongation
of the systolic ejection time, and resolved promptly with
discontinuation of the infusions of CK-1827452.
-- In addition, at HFSA, Cytokinetics also presented three poster
presentations relating to preclinical data from its cardiovascular
program:
-- The first poster entitled, "In Vitro and In Vivo
Characterization of CK-1827452, a Selective Cardiac Myosin
Activator," contained data demonstrating that CK-1827452,
consistent with its mechanism of action, increases
contractility in myocytes without increasing calcium and
significantly increases cardiac fractional shortening in normal
rats, normal dogs and rats with heart failure.
-- The second poster entitled, "Activating Cardiac Myosin, a Novel
Inotropic Mechanism to Improve Cardiac Function in Conscious
Dogs with Congestive Heart Failure," provided supporting data
on the preclinical profile of CK-1827452. This poster
demonstrated that CK-1827452 increased stroke volume and left
ventricular fractional shortening in normal dogs and increased
cardiac output, stroke volume and left ventricular fractional
shortening in dogs with heart failure. In association with the
improvement of left ventricular systolic performance, left
ventricular filling pressures, heart rate and total peripheral
resistance decreased in the dogs with heart failure. Expressed
as a percentage change from baseline, the effects of CK-1827452
in dogs with heart failure were generally greater than those
observed in normal dogs.
-- The third poster entitled, "Cardiac Myosin Activator,
CK-1316719, Increases Myofibril ATPase Activity and Myocyte
Contractility in a Rat Model of Heart Failure," provided data
further validating the mechanism of another of Cytokinetics'
cardiac myosin activators.
-- In August, Cytokinetics announced the initiation of a Phase I
clinical trial evaluating the pharmacokinetic profile of CK-1827452
when administered orally to healthy volunteers. Pharmacokinetic
data from the recently completed Phase I clinical trial of the
intravenous formulation of CK-1827452 in healthy volunteers suggests
that the half-life of CK-1827452 may be sufficient to support
development of an oral dosing formulation.
-- During the quarter, GlaxoSmithKline (GSK) closed enrollment, after
enrolling a total of 50 patients, in a two-stage Phase II clinical
trial evaluating ispinesib as a treatment for patients with locally
advanced or metastatic breast cancer. 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,
RECIST) out of 33 evaluable patients. The 3 patients had maximum
decreases in tumor size ranging from 46% to 68% with the duration of
response ranging from 7.1 weeks to 13.4 weeks. The most common
adverse event was Grade 4 neutropenia.
-- GSK continued to treat a patient in a Phase II clinical trial
evaluating ispinesib as a second-line treatment for patients with
advanced ovarian cancer.
-- The National Cancer Institute (NCI) continued to treat patients in a
Phase II clinical trial of ispinesib in patients with hepatocellular
cancer, and also continued to treat patients in Phase I clinical
trials designed to evaluate the safety, tolerability and
pharmacokinetics of ispinesib in patients with hematologic
malignancies (i.e., acute leukemia, chronic myelogenous leukemia or
advanced myelodysplastic syndromes) and with solid tumors. In
addition, the NCI concluded enrollment in two of its Phase II
clinical trials evaluating ispinesib as monotherapy in patients with
melanoma and in patients with hormone-refractory prostate cancer.
-- Cytokinetics continued to enroll patients in a Phase I/II clinical
trial of SB-743921, evaluating patients with non-Hodgkin's lymphoma
(NHL), in connection with an expanded development program for SB-
743921. This trial is an open-label, non-randomized clinical trial
designed 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, first without and
then with the administration of granulocyte colony stimulating
factor (GCSF) in patients with NHL.
-- In October, interim data from a Phase II clinical trial for
ispinesib in recurrent and/or metastatic head and neck squamous cell
carcinoma (RMHNSC) was presented at the Annual Meeting of the
European Society of Medical Oncology (ESMO). This clinical trial
was conducted by the NCI in association with GSK. This Phase II
clinical trial was designed to evaluate the safety and efficacy of
ispinesib administered at 18 mg/m2 as a one-hour intravenous
infusion once every 21 days in patients with RMHNSC, who had
received no more than one prior chemotherapy regimen. This two-
stage clinical trial was designed to require a minimum of 1
confirmed partial or complete response out of 19 evaluable patients
in Stage 1 in order to proceed to Stage 2. The clinical trial's
primary endpoint was response rate as determined using RECIST
criteria. A total of 21 patients were enrolled; one patient did not
receive ispinesib due to disease progression prior to treatment, and
another was evaluable for safety but not efficacy. At the interim
analysis after Stage 1 of this clinical trial, the criteria for
advancement to Stage 2 were not satisfied. The best overall
response to date in this clinical trial was disease stabilization,
which was observed in 5 of the 19 patients evaluable for efficacy at
cycle 2. Overall, median time to disease progression was 5.9 (95% CI
5.4-10.0) weeks. The safety and pharmacokinetics of ispinesib in
this clinical trial were evaluated in 20 of the patients enrolled in
the trial. The most common grade 3 or greater adverse event was
neutropenia, occurring in 55% of patients treated. Two patients
died on study. One death in a patient with a non-neutropenic
infection (grade 3) was attributed to progressive disease, the
other, in a patient with four days of grade 3-4 neutropenia, was
attributed to pneumonia.
Financials
Revenues from research and development collaborations for the third
quarter of 2006 were $0.1 million, compared to $1.9 million in the third
quarter of 2005. Revenues for both the third quarter of 2006 and 2005 were
largely derived from our research collaboration with GSK. The decline in
collaborative research revenues for the third quarter of 2006, as compared
to the same period in 2005, was primarily due to reductions in license fee,
full time equivalent and patent reimbursement revenues of $1.5 million by
GSK and a reduction in collaboration revenue of $0.3 million, as a result
of the expiration of the research term under our collaboration agreement
with AstraZeneca in December of 2005. The AstraZeneca collaboration
agreement was formally terminated in August 2006.
Total research and development (R&D) expenses for the third quarter of
2006 were $12.5 million, compared to $9.3 million for the third quarter of
2005. The increase in R&D expenses in the third quarter of 2006, over the
same period in 2005, was primarily due to increased spending related to the
manufacture of clinical supply and other clinical outsourcing costs as
Cytokinetics advanced its drug candidates for the treatment of
cardiovascular disease and cancer through clinical trials, along with
increased laboratory expenses and expenses related to compensation and
benefits, including charges for stock-based compensation.
Total general and administrative (G&A) expenses for the third quarter
of 2006 were $3.6 million, compared to $3.3 million in the third quarter of
2005. The increased spending in the third quarter of 2006, compared to the
same period in 2005, was primarily due to increased expenses related to
compensation and benefits, including charges for stock-based compensation,
which were partially offset by lower legal fees.
The net loss for the three months ended September 30, 2006, was $14.9
million, or $0.41 per share, compared to a net loss for the same period in
2005 of $10.1 million, or $0.35 per share.
Cytokinetics also reported results from its operations for the nine
months ended September 30, 2006. Revenues from research, development
collaborations for the nine months ended September 30, 2006 were $3.0
million, compared to $6.8 million for the same nine month period in 2005.
The decline in collaborative research revenues for the first nine months of
2006, compared to the same period in 2005, was primarily due to a decrease
in license fee, full time equivalent and patent reimbursement revenues of
$2.9 million by GSK and a reduction in collaboration revenue of $0.9
million, as a result of the expiration of the research term under our
collaboration agreement with AstraZeneca in December of 2005. The
AstraZeneca collaboration agreement was formally terminated in August 2006.
Total R&D expenses for the nine months ended September 30, 2006 were
$36.2 million, compared to $29.8 million for the same nine month period in
2005. The increased spending in the first nine months of 2006, over the
same period in 2005, was primarily due to increased outsourcing costs
related to the manufacturing of clinical supplies and ongoing clinical
trials for Cytokinetics' cardiovascular and oncology programs, along with
higher laboratory and personnel expenses, including charges for stock-based
compensation.
Total G&A expenses for the nine months ended September 30, 2006 were
$11.1 million, compared to $9.9 million for the same nine month period in
2005. The increased spending in the first nine months of 2006, over the
same period in 2005, was primarily due to increased personnel expenses,
including charges for stock-based compensation, which were slightly offset
by lower legal fees.
The net loss for the nine months ended September 30, 2006, was $41.2
million, or $1.15 per share, compared to a net loss for the same nine month
period in 2005 of $31.2 million, or $1.09 per share.
Updated Company Milestones
Oncology
Ispinesib (SB-715992):
-- Data are anticipated from Stage 2 of GSK's Phase II clinical trial
of second- or third-line therapy in patients with locally advanced
or metastatic breast cancer by the end of 2006.
-- Data are anticipated from Stage 1 of GSK's Phase II clinical trial
of second-line therapy in patients with ovarian cancer by the end of
2006.
-- Additional Phase Ib clinical trial data evaluating ispinesib in
combination with capecitabine are planned to be presented in
November at the EORTC-NCI-AACR meeting in Prague, Czech Republic.
-- Additional Phase Ib clinical trial data evaluating ispinesib in
combination with carboplatin are anticipated in the first half of
2007.
-- Data from Stage 1 of the NCI's Phase II clinical trial in patients
with melanoma are anticipated to be available by the end of 2006.
-- Data from Stage 1 of the NCI's Phase II clinical trial of patients
with hormone-refractory prostate cancer are anticipated to be
available by the end of 2006.
-- Initiation of the NCI's Phase II clinical trial evaluating ispinesib
as monotherapy in patients with renal cell cancer is anticipated by
the end of 2006.
-- Initiation of the NCI's Phase I clinical trial evaluating ispinesib
as monotherapy in pediatric patients with relapsed or refractory
solid tumors is anticipated by the end of 2006.
SB-743921:
-- Interim data are anticipated from our Phase I/II clinical trial
evaluating SB-743921 in the treatment of patients with NHL in the
first half of 2007.
GSK-923295:
-- A regulatory filing is anticipated by GSK in early 2007 to allow
initiation of first-in-human clinical trials in 2007.
The clinical trial milestones for the oncology program described above,
with the exception of SB-743921, are based on information provided by GSK
or the NCI. The occurrence of these events is outside of Cytokinetics'
control.
Cardiovascular
CK-1827452:
-- Initiation of Phase II clinical trials program with CK-1827452 is
anticipated by the end of 2006.
-- Phase I clinical trial data evaluating the oral bioavailability of
CK-1827452 are anticipated by the end of 2006.
Conference Call and Webcast Information
Members of the Cytokinetics management team will review third quarter
results via webcast and conference call today at 4:30 p.m. Eastern Time. To
access the live webcast, please log-on in the Investor Center section of
Cytokinetics' website at http://www.cytokinetics.com. Investors, members of the
news media and the general public may access the call by dialing either
(866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078
(International) and typing in the passcode 9299494.
An archived replay of the webcast will be available via Cytokinetics'
website until November 26, 2006. The replay will also be available via
telephone by dialing (800) 642-1687 (United States and Canada) or (706)
645-9291 (International) and typing in the passcode 9299494 from October
26, 2006 at 6:45 p.m. Eastern Time until November 3, 2006.
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. Under a
strategic alliance established in 2001, Cytokinetics and GSK are
collaborating to 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 and Cytokinetics
is conducting a Phase I/II trial of SB-743921 in non-Hodgkin's lymphoma.
Cytokinetics' unpartnered cardiovascular disease program is the second
program to leverage the company's expertise in cytoskeletal pharmacology.
Cytokinetics recently completed a Phase I clinical trial with CK-1827452, a
novel small molecule cardiac myosin activator, for the intravenous
treatment of heart failure and also is advancing 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 relating to the
expected initiation, timing, scope and results of clinical trials within
Cytokinetics' and its partners' clinical development and research programs,
including a potential regulatory filing by GSK for GSK- 923295, research
and development milestones, anticipated dates of release of data from
clinical trials and upcoming presentations of clinical trial results, our
financial guidance, including expected revenues and R&D and G&A expenses
for 2006, the potential benefits of Cytokinetics' drug candidates and
potential drug candidates, the enabling capabilities of Cytokinetics'
proprietary technologies and the benefits of data obtained from completed
clinical trials. 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 decisions by GSK
or the NCI to postpone or discontinue research and/or development efforts
for one or more compounds or for GSK to discontinue funding of such efforts
under Cytokinetics' collaboration with GSK, difficulties or delays in
patient enrollment for clinical trials, unexpected adverse side effects or
inadequate therapeutic efficacy of Cytokinetics' 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 or trade
secret protection for Cytokinetics' intellectual property, Cytokinetics'
ability to obtain additional financing if necessary and unanticipated
research and development and other costs),and changing standards of care
and the introduction by others of products or alternative therapies for the
treatment of indications currently or potentially targeted by CK-1827452 or
Cytokinetics' other drug candidates and potential drug candidates. For
further information regarding these and other risks related to
Cytokinetics' business, investors should consult Cytokinetics' filings with
the Securities and Exchange Commission.
Condensed Statement of Operations
(in thousands, except share and per share data)
(unaudited)
Three Months Ended Nine Months Ended
September September September September
30, 2006 30, 2005 30, 2006 30, 2005
Revenues:
Research and development $106 $1,155 $1,572 $4,668
License revenues - 700 1,400 2,100
Total revenues 106 1,855 2,972 6,768
Operating Expenses:
Research and development 12,535 9,259 36,199 29,835
General and administrative 3,572 3,325 11,131 9,870
Total operating expenses 16,107 12,584 47,330 39,705
Operating loss: (16,001) (10,729) (44,358) (32,937)
Interest and other income 1,215 756 3,572 2,156
Interest and other expense (134) (128) (383) (390)
Net loss $(14,920) $(10,101) $(41,169) $(31,171)
Net loss per common share
- basic and diluted $(0.41) $(0.35) $(1.15) $(1.09)
Weighted average shares
used in computing net
loss per common share
- basic and diluted 36,729,400 28,588,539 35,793,082 28,494,287
Condensed Balance Sheet Data
(in thousands)
(unaudited)
September 30, December 31,
2006 2005
Assets
Cash and cash equivalents $48,214 $13,515
Short term investments 40,478 62,697
Other current assets 2,721 2,652
Total current assets 91,413 78,864
Property and equipment, net 7,178 6,178
Restricted investments 5,204 5,172
Other assets 854 1,247
Total assets $104,649 $91,461
Liabilities and stockholders' equity
Current liabilities $12,405 $11,264
Long-term obligations 6,654 6,636
Stockholders' equity 85,590 73,561
Total liabilities and stockholders'
equity $104,649 $91,461
SOURCE Cytokinetics, Incorporated
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Related links:
http://www.cytokinetics.com/
CONTACT:
Sharon Surrey-Barbari, SVP, Finance & CFO of
Cytokinetics, Incorporated, +1-650-624-3000; or investors, Clay
A. Kramer, or media, Justin Jackson, both of Burns McClellan,
Inc., +1-212-213-0006
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