Cytokinetics Provides Clinical Trials Update for Ispinesib (SB-715992)

[Guest guest]

This drug is mainly being tested for Breast cancer, but the NCI is now

opening up phase I DRUG ESCALATION trials for this drug for patients with

AML, CML and advanced Myelodysplastic syndromes. So, there's even more

hope.

Good reading!

Cheryl-Anne

Cytokinetics Provides Clinical Trials Update for Ispinesib (SB-715992)

-- Drug Candidate Demonstrates Sufficient Anti-Tumor Activity to Proceed in

Its Phase II Locally Advanced or Metastatic Breast Cancer Clinical Trial

-- Drug Candidate Does Not Demonstrate Sufficient Anti-Tumor Activity to

Proceed in the Platinum-Refractory Arm of Its Phase II Non-Small Cell Lung

Cancer Clinical Trial

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SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Sep 27, 2005--Cytokinetics,

Incorporated (Nasdaq: CYTK) announced the results from planned interim

analyses of two Phase II clinical trials of ispinesib administered as

monotherapy in the treatment of patients with locally advanced or metastatic

breast cancer and the treatment of patients with platinum-refractory

non-small cell lung cancer, both Phase II clinical trials being conducted by

its alliance partner, GlaxoKline (GSK).

In the treatment of locally advanced or metastatic breast cancer patients,

ispinesib has demonstrated sufficient clinical activity to proceed to the

next stage of the Phase II clinical trial. In the platinum-refractory

treatment arm of the non-small cell lung cancer trial, ispinesib did not

demonstrate sufficient clinical activity to proceed to the next stage of the

Phase II clinical trial for this stratum. A second platinum-sensitive

patient treatment arm in that trial continues. Both clinical trials employ a

conventional Green-Dahlberg design which specifies that the advancement to

the second stage requires the satisfaction of pre-defined efficacy criteria.

These clinical trials are the first to reach the stage of interim data

analysis from a broad Phase II program of ispinesib that is designed to

determine potential anti-cancer activity and relevant clinical effect in

nine Phase II clinical trials encompassing multiple tumor types under the

sponsorship of GSK or the National Cancer Institute (NCI).

In an ongoing 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 has recurred

or progressed despite treatment with anthracyclines and taxanes, the drug

candidate has satisfied the criteria for advancement to the next stage. This

clinical trial is now planned to proceed to full enrollment of 55 evaluable

patients. This clinical trial is designed to require a minimum of 3

confirmed partial or complete responses out of 30 evaluable patients to

proceed to stage 2. The trial's primary endpoint is response rate as

determined using RECIST criteria. The best overall responses observed to

date have been partial responses observed in 3 patients. All patients

enrolled to date in this clinical trial have had metastatic disease. Interim

results from this clinical trial have been accepted for presentation at the

28th San Breast Cancer Symposium to be held from December 7-10,

2005.

In a Phase II clinical trial designed to evaluate the safety and efficacy of

ispinesib in the second-line treatment of patients with either

platinum-sensitive or platinum-refractory non-small cell lung cancer, the

drug candidate has not satisfied the criteria for advancement to the next

stage in the platinum-refractory treatment arm. The platinum-sensitive

treatment arm continues to treat patients but has not yet reached the

interim analysis stage. This clinical trial is designed to require a minimum

of 1 confirmed partial or complete response out of 20 evaluable patients in

a treatment arm to proceed to stage 2 in that treatment arm. The trial's

primary endpoint is response rate as determined using RECIST criteria. The

best overall responses observed to date in the platinum-refractory treatment

arm of this clinical trial have been disease stabilization observed in 5 of

20 evaluable patients. Overall, median time to disease progression was 6

weeks; in the 5 patients whose best response was stable disease, median time

to progression was 12 weeks. The safety and pharmacokinetics of ispinesib in

the platinum-refractory arm of this clinical trial appear comparable to that

observed from its Phase I clinical trial at equivalent doses. Data from the

platinum-sensitive treatment arm of this clinical trial are expected to be

announced by the end of 2005.

" We are pleased to share the data recently emerging from our ongoing Phase

II clinical trials program with ispinesib, " stated Sabry, M.D., Ph.D.,

President and Chief Executive Officer. " Today's announcements are

encouraging as we have now observed measurable anti-cancer activity with

this mechanism in the second-line and third-line treatment of locally

advanced or metastatic breast cancer patients and the first evidence of

confirmed tumor shrinkage due to treatment of cancer patients with

ispinesib. "

" We are now seeing evidence of potential clinical benefit of ispinesib

demonstrated in the form of tumor shrinkage in locally advanced or

metastatic breast cancer patients, " said Dr Oliff, Senior Vice

President of the Microbial, Musculoskeletal and Proliferative Diseases

Center for Excellence in Drug Discovery at GlaxoKline. " We look forward

to further data arising out of our broad clinical trials program designed to

evaluate the full potential of this novel drug candidate. "

Conference Call / Webcast

Cytokinetics will host a conference call on Tuesday, September 27, 2005 at

6:00 p.m. Eastern Time. The conference call will be simultaneously webcast

and will be accessible in the Investor Relations section of Cytokinetics'

website at www.cytokinetics.com. The live audio of the conference call will

also be accessible via telephone to investors, members of the news media and

the general public by dialing either (866) 999-CYTK (2985) (United States

and Canada) or (706) 679-3078 (International) and typing in the passcode

9953889. An archived replay of the webcast will be available via

Cytokinetics' website until October 4, 2005. 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 9953889 from

September 27, 2005 at 7:00 p.m. Eastern Time until October 4, 2005.

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.

Clinical Trials Status for Ispinesib

Ispinesib is the subject of a broad clinical trials program under the

sponsorship of GSK and the NCI. GSK is conducting 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 platinum-sensitive

non-small cell lung cancer and one evaluating ispinesib as second-line

treatment for patients with advanced ovarian cancer. In addition, GSK is

continuing three dose-escalating Phase Ib clinical trials. Each of these

clinical trials is 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 NCI, in

collaboration with GSK, continues patient enrollment in five additional

Phase II clinical trials evaluating the potential efficacy of ispinesib in

the second-line treatment of patients with colorectal cancer, in the

first-line treatment of patients with hepatocellular cancer, in the

first-line treatment of patients with melanoma, in the first-line or

second-line treatment of patients with head and neck cancers, and in the

second-line treatment of patients with hormone-refractory prostate cancer.

In addition, the NCI plans to initiate an additional Phase II clinical trial

to evaluate the potential efficacy of ispinesib as second-line treatment of

patients with renal cell cancer. The NCI also continues patient enrollment

in two additional Phase I clinical trials designed to evaluate the safety,

tolerability and pharmacokinetics of ispinesib on an alternative dosing

schedule. One clinical trial is enrolling patients with advanced solid

tumors that have failed to respond to all standard therapies and the other

clinical trial is enrolling patients with acute leukemia, chronic

myelogenous leukemia or advanced myelodysplastic syndromes.

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 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 GlaxoKline 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. GlaxoKline is conducting Phase II and Phase Ib clinical

trials for ispinesib (SB-715992) and a Phase I clinical trial for SB-743921,

each a drug candidate that has emerged from the strategic alliance.

Cytokinetics' heart failure program is the second program to leverage the

company's expertise in cytoskeletal pharmacology. Cytokinetics recently

initiated a Phase I clinical trial with CK-1827452, a novel small molecule

cardiac myosin activator, for the treatment of heart failure. Additional

information about Cytokinetics can be obtained at www.cytokinetics.com.