DELAWARE | 000-50633 | 94-3291317 | ||
(State or other jurisdiction of incorporation) |
(Commission File Number) | (IRS Employer Identification No.) |
ITEM 2.02. RESULTS FROM OPERATIONS AND FINANCIAL CONDITION | ||||||||
ITEM 9.01. FINANCIAL STATEMENTS AND EXHIBITS | ||||||||
SIGNATURES | ||||||||
EXHIBIT INDEX | ||||||||
EXHIBIT 99.1 |
Exhibit No. | Description | |
99.1
|
Press Release, dated July 27, 2006. |
CYTOKINETICS, INCORPORATED | ||||
By: | /s/ James H. Sabry | |||
James H. Sabry | ||||
Chief Executive Officer |
Cytokinetics, Incorporated
|
Burns McClellan, Inc. | |
Sharon Surrey-Barbari
|
Clay A. Kramer (investors) | |
SVP, Finance & CFO
|
Justin Jackson (media) | |
(650) 624-3000
|
(212) 213-0006 |
| In June, Cytokinetics announced that its first-in-humans Phase I clinical trial evaluating CK-1827452 (CK-452), a novel cardiac myosin activator, administered intravenously, demonstrated statistically significant and clinically relevant increases in ejection fraction, fractional shortening and systolic ejection time, which are measures of increases in cardiac function. The clinical trial was designed as a double-blind, randomized, placebo-controlled, dose-escalation trial conducted to investigate the safety, tolerability, pharmacokinetics and pharmacodynamic profile of a six-hour infusion of CK-452 in healthy volunteers. The maximum tolerated dose (MTD) was determined to be 0.5 mg/kg/hr for the six-hour infusion in healthy volunteers. At the MTD, CK-452 was well-tolerated when compared to placebo. Across the dosing levels evaluated in this clinical trial, infusions of CK-452 were characterized by linear, dose-proportional pharmacokinetics and produced dose-dependent pharmacodynamic effects. 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 a hyper-contractile state of the myocardium and were resolved promptly with discontinuation of the infusions of CK-452. | ||
| In June, GlaxoSmithKline (GSK) presented data from a Phase Ib combination clinical trial of ispinesib at the 2006 Annual Meeting of the American Society of Clinical Oncology (ASCO) suggesting ispinesib, a kinesin spindle protein (KSP) inhibitor, on a once every 21-day schedule, has an acceptable tolerability profile and no pharmacokinetic interactions when used in combination with carboplatin, a common chemotherapeutic agent used in patients suffering from advanced solid tumors. At the optimally tolerated regimen, ispinesib concentrations were not affected by carboplatin. The best response was a partial response at cycle 2 in one patient with breast cancer; a total of 13 patients (46%) had a best response of stable disease with durations ranging from 3 to 9 months. | ||
| At ASCO, the National Cancer Institute (NCI) presented data from a Phase I dose escalation trial of ispinesib, administered days 1 through 3 of a 21-day cycle, in 27 patients with various advanced solid tumors. The primary objectives of this clinical trial were to assess the safety and tolerability of ispinesib and to determine the dose limiting toxicity (DLT) and MTD at this dosing regimen. The most common grade 3 and 4 toxicities at doses |
ranging between 4 mg/m2 and 8 mg/m2 were neutropenia and at some doses leukopenia. As a result, 6 mg/m2 was further evaluated as the 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. | |||
| Also, at ASCO, the NCI presented data from a Phase II clinical trial evaluating the response rate of patients with metastatic colorectal cancer treated with ispinesib as a monotherapy. Patients were randomized to receive ispinesib at 7 mg/m 2 on days 1, 8, and 15 of a 28-day schedule (Arm A) or 18 mg/m 2 every 21 days (Arm B). The authors concluded that ispinesib did not manifest an objective response rate on the two schedules evaluated in heavily pretreated colorectal cancer patients. The most common grade 3 and 4 toxicities in Arm A included neutropenia, nausea, vomiting and fatigue. The most common grade 3 and 4 toxicity in Arm B was neutropenia, only one of which was febrile. The authors concluded that the weekly dose given in Arm A appeared to have a more favorable toxicity profile compared to the dose given in Arm B. | ||
| GSK continued to treat patients in two Phase II clinical trials, one evaluating ispinesib as a second-line treatment for patients with advanced ovarian cancer and the second evaluating ispinesib as the second- or third-line treatment of patients with metastatic breast cancer. The breast cancer trial is evaluating patients in Stage 2 of a two-stage design Phase II clinical trial. In Stage 1 of the breast cancer trial the best overall responses observed were 3 partial responses out of 33 evaluable patients as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). The three 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. In addition, GSK continues to treat patients in a Phase Ib clinical trial evaluating ispinesib in combination with capecitabine. | ||
| During the quarter, the NCI concluded Stage 1 enrollment of four Phase II clinical trials, each of which has a two-stage design. The first clinical trial is evaluating ispinesib in the first- or second-line treatment of patients with head and neck cancer. The second clinical trial is evaluating ispinesib in the first-line treatment of patients with melanoma who may have received adjuvant immunotherapy but no chemotherapy. The third clinical trial is evaluating ispinesib in the first-line treatment of patients with hepatocellular cancer. The primary endpoint of these three clinical trials is objective response as determined using the RECIST criteria. The fourth trial is evaluating ispinesib in the second-line treatment of patients with hormone-refractory prostate cancer. The primary endpoint of this trial is objective response as determined by blood serum levels of the tumor mass marker Prostate Specific Antigen. | ||
| At ASCO, GSK presented in an oral presentation, data from a Phase I clinical trial evaluating the tolerability and pharmacokinetics of SB-743921 (SB-921), Cytokinetics second KSP inhibitor. The primary objectives of this clinical trial were to determine the DLTs and to establish the MTD of SB-921 administered intravenously on a once every 21-day schedule; secondary objectives included assessment of the safety and tolerability of SB-921, in order to characterize the pharmacokinetics of SB-921 on this schedule and to make a preliminary assessment of the antitumor activity of SB-921. The recommended Phase II dose of SB-921 on the 21-day 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. Disease stabilization (range 9-45 weeks) was observed in 7 patients. A patient with cholangiocarcinoma had a confirmed partial response at the MTD at cycle 10. | ||
| Cytokinetics continues to enroll patients in a Phase I/II clinical trial of SB-921, evaluating patients with non-Hodgkins lymphoma (NHL), in connection with an expanded development program for SB-921. This trial is an open-label, non-randomized clinical trial designed to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of SB-921, 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 June, Cytokinetics announced the extension of the research term under its strategic alliance with GSK for an additional year to continue research activities focused towards centromere-associated protein E (CENP-E). This research term extension will positively contribute to the further translational research activities underlying the development activities of GSK-923295 or GSK-295, a potential drug candidate that targets CENP-E. CENP-E is a mitotic kinesin directly involved in coupling the mechanics of mitosis with the mitotic checkpoint signaling machinery, regulating cell-cycle transition from metaphase to anaphase. CENP-E is also essential for prometaphase chromosome movements that contribute to metaphase chromosome alignment. These processes are essential to cell proliferation. |
| Additional data are anticipated from Stage 2 of GSKs Phase II clinical trial of second- or third-line therapy in patients with locally advanced or metastatic breast cancer in the second half of 2006. | ||
| Data are anticipated from Stage 1 of GSKs Phase II clinical trial of second-line therapy in patients with ovarian cancer in the second half of 2006. | ||
| Additional data are anticipated from GSKs Phase Ib clinical trial evaluating ispinesib in combination with capecitabine in the second half of 2006. | ||
| Interim data from Stage 1 of the NCIs Phase II clinical trial in patients with melanoma are anticipated to be available in the second half of 2006. | ||
| Data from the NCIs Phase II clinical trial of patients with head and neck cancer are planned to be presented at the 31st Congress of the European Society for Medical Oncology (ESMO) in September in Istanbul, Turkey. | ||
| Interim data from Stage 1 of the NCIs Phase II clinical trial of patients with hepatocellular cancer are anticipated to be available in the second half of 2006. | ||
| Interim data from Stage 1 of the NCIs Phase II clinical trial of patients with hormone-refractory prostate cancer are anticipated to be available in the second half of 2006. | ||
| Initiation of the NCIs Phase II clinical trial evaluating ispinesib as monotherapy in patients with renal cell cancer is anticipated in the second half of 2006. | ||
| Initiation of the NCIs Phase I clinical trial evaluating ispinesib as monotherapy in pediatric patients with relapsed or refractory solid tumors is anticipated in the second half of 2006. |
| A regulatory filing is anticipated by GSK in early 2007 to allow initiation of first time in human clinical trials in the first half of 2007. |
| Data from the Phase I clinical trial of CK-452 are planned to be presented at a session entitled Recent and Late Breaking Trials at the 10th Annual Meeting of the Heart Failure Society of America (HFSA) on Wednesday, September 13, 2006 in Seattle, Washington. The presentation will be made by John R. Teerlink, M.D., F.A.C.C., F.A.H.A., F.E.C.S, Associate Professor of Medicine at the University of California, San Francisco, and Director of the Heart Failure Clinic, Veterans Affairs Medical Center, San Francisco. Dr. Teerlink is a Co-Principal Investigator and responsible for the echocardiographic analysis for the Phase I clinical trial. | ||
| Initiation of a Phase II clinical trials program for CK-452 is anticipated in the second half of 2006. | ||
| Initiation of a Phase I oral bioavailability trial of CK-452 is anticipated in the second half of 2006. |
Three Months Ended | Six Months Ended | |||||||||||||||
June 30, | June 30, | June 30, | June 30, | |||||||||||||
2006 | 2005 | 2006 | 2005 | |||||||||||||
Revenues: |
||||||||||||||||
Research and development |
$ | 746 | $ | 1,641 | $ | 1,466 | $ | 3,513 | ||||||||
License revenues |
700 | 700 | 1,400 | 1,400 | ||||||||||||
Total revenues |
1,446 | 2,341 | 2,866 | 4,913 | ||||||||||||
Operating Expenses: |
||||||||||||||||
Research and development |
11,897 | 10,039 | 23,164 | 20,576 | ||||||||||||
General and administrative |
3,938 | 3,403 | 7,560 | 6,546 | ||||||||||||
Total operating expenses |
15,835 | 13,442 | 30,724 | 27,122 | ||||||||||||
Operating loss: |
(14,389 | ) | (11,101 | ) | (27,858 | ) | (22,209 | ) | ||||||||
Interest and other income |
1,228 | 688 | 2,357 | 1,400 | ||||||||||||
Interest and other expense |
(125 | ) | (127 | ) | (248 | ) | (261 | ) | ||||||||
Net loss |
$ | (13,286 | ) | $ | (10,540 | ) | $ | (25,749 | ) | $ | (21,070 | ) | ||||
Net loss per common share basic and diluted |
$ | (0.37 | ) | $ | (0.37 | ) | $ | (0.73 | ) | $ | (0.74 | ) | ||||
Weighted average shares used in computing net loss per
common share basic and diluted |
36,375,619 | 28,513,959 | 35,317,352 | 28,447,164 |
June 30, | December 31, | |||||||
2006 | 2005 | |||||||
Assets |
||||||||
Cash and cash equivalents |
$ | 49,766 | $ | 13,515 | ||||
Short term investments |
45,155 | 62,697 | ||||||
Other current assets |
2,669 | 2,652 | ||||||
Total current assets |
97,590 | 78,864 | ||||||
Property and equipment, net |
5,920 | 6,178 | ||||||
Restricted investments |
5,100 | 5,172 | ||||||
Other assets |
968 | 1,247 | ||||||
Total assets |
$ | 109,578 | $ | 91,461 | ||||
Liabilities and stockholders equity |
||||||||
Current liabilities |
$ | 10,150 | $ | 11,264 | ||||
Long-term obligations |
6,136 | 6,636 | ||||||
Stockholders equity |
93,292 | 73,561 | ||||||
Total liabilities and stockholders equity |
$ | 109,578 | $ | 91,461 | ||||