Cytokinetics Announces Phase I Results for SB-715992 Presented at the 2004 Annual Meeting of the American Society of Clinical Oncology

Safety and Tolerability Profile of SB-715992 Supports Initiation of Broad Phase II Program

Monday June 7, 9:01 am ET

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--June 7, 2004-- Cytokinetics, Inc. (Nasdaq:CYTK - News) announced today that the results of two Phase I studies for SB-715992 conducted by GlaxoSmithKline were presented in oral and poster presentations at the 2004 Annual Meeting of the American Society of Clinical Oncology (ASCO) in New Orleans. The presentations focused on the safety and tolerability of SB-715992, a novel small molecule inhibitor of kinesin spindle protein (KSP), a mitotic kinesin protein essential for proper cell division. SB-715992 is the lead drug candidate in clinical development arising from a broad strategic collaboration between Cytokinetics and GlaxoSmithKline to discover, develop and commercialize novel small molecule therapeutics targeting human mitotic kinesins for applications in the treatment of cancer and other diseases. GlaxoSmithKline has initiated a broad Phase II clinical trial program for SB-715992.

The Phase I trials were open-label, non-randomized, dose-finding trials designed to study the safety, tolerability, pharmacokinetic and pharmacodynamic profile of SB-715992. In total, 75 patients with multiple advanced solid tumors were enrolled and treated with SB-715992 in these trials. The more common tumor types were colon, renal cell carcinoma, sarcoma, breast and lung cancer. All enrolled patients had relapsed or had been refractory to previous treatment with a variety of standard chemotherapeutic regimens that included, but were not limited to, drugs such as irinotecan, topotecan, gemcitabine, paclitaxel, vinblastine, and cyclophosphamide.

The presentation entitled "Phase I trial of novel kinesin spindle protein (KSP) inhibitor SB-715992 IV days 1, 8, 15, q 28 days" was presented on June 6, 2004 by Dr. Howard Burris, The Sarah Cannon Cancer Center, Nashville, TN. The principle objective of this trial was to determine the safety profile and tolerability of SB-715992. Within this dose-escalating trial, 30 patients received doses of SB-715992 intravenously on days 1, 8 and 15 over a 28-day period. By study design, dose escalation continued until dose-limiting toxicities were observed. The dose limiting toxicity was neutropenia preventing day 15 dosing in 2 of 3 patients. Neurotoxicities and alopecia were not observed; minimal GI toxicities with a single event of greater than Grade 2 were reported and were not considered dose-limiting. SB-715992 was well-tolerated in this advanced disease setting at all dose levels. Prolonged disease stabilization, ranging from 16 to more than 32 weeks, was observed in 8 of 30 patients representing a variety of tumor types.

A poster entitled "Phase I trial of novel kinesin spindle protein (KSP) inhibitor SB-715992 IV q 21 days" was presented on June 7, 2004 by Dr. Quincy Chu, Cancer Therapy and Research Center (CTRC), San Antonio, TX. The principle objective of this trial was also to determine the safety profile and tolerability of SB-715992 but under a different dosing schedule than that used in the Phase I trial mentioned above. Within this dose-escalating trial, 45 patients received doses of SB-715992 intravenously every 21 days. By study design, dose escalation continued until dose limiting toxicities were observed. The dose limiting toxicity was neutropenia for five or more days. In this study, SB-715992 was well-tolerated in this advanced disease setting at all dose levels. Prolonged disease stabilization, ranging from 7 to 43 weeks, was observed in 15 of 45 patients in a variety of tumor types. Neurotoxicities were not prevalent; alopecia was not reported. Based on the results of these trials, the 18 mg/m2 dose level was selected as a recommended Phase II dose for this dosing schedule.