Cytokinetics Inc. will be footing more of the bill to develop two drugs it has partnered with GlaxoSmithKline plc per terms of an amendment to the companies' five-year collaboration.
Investors reacted negatively to the news, with Cytokinetics' shares (NASDAQ:CYTK) sliding 30 cents on Tuesday to close at $6.99. But management at South San Francisco-based Cytokinetics said the increased responsibility gives Cytokinetics a more prominent role in the kinesin spindle protein (KSP) inhibitors' development.
The amended terms call for the company to assume control of the costs and activities around ispinesib (SB-715992) and SB-743921, subject to GSK's option to resume responsibility for some or all development and commercialization activities associated with each of them. If the London pharmaceutical firm exercises an option for a particular drug candidate, it will pay Cytokinetics an option fee equal to the costs it independently incurred for that product, plus a premium intended to compensate the expense of capital associated with such costs.
Going forward, Cytokinetics plans to conduct a focused development program for ispinesib in metastatic breast cancer to supplement past Phase I and II trials sponsored by GSK that have demonstrated the drug's clinical activity in that setting and lung cancer, as well as its potential for combination treatment with standard chemotherapeutics. Last year, negative interim data from a Phase II study in non-small-cell lung cancer patients prompted the partners to cancel it early. (See BioWorld Today, Sept. 29, 2005.)
Cytokinetics is considering plans to conduct trials in advanced breast cancer patients next year to define ispinesib's clinical activity profile in that indication ahead of initiating a Phase III study for the second-line treatment of advanced breast cancer. Positive Phase II data showed that ispinesib as a monotherapy led to three partial responses among 33 evaluable patients in a study conducted by GSK. Those three patients had maximum decreases in tumor size ranging from 46 percent to 68 percent, with the durations of response ranging from 7.1 weeks to 13.4 weeks.
Concurrent with that supplemental advanced breast cancer program for ispinesib, the National Cancer Institute is continuing Phase I and II trials in a range of indications including head and neck, prostate, colorectal, liver and kidney cancers, as well as melanoma and leukemia. In addition, Cytokinetics is continuing an ongoing Phase I/II trial of SB-743921 in non-Hodgkin's lymphoma, which began earlier this year. The open-label trial is designed to investigate the product's safety and tolerability, as well as its pharmacokinetic and pharmacodynamic profiles, when administered as a one-hour infusion on days one and 15 of a 28-day schedule, first without and then with granulocyte-colony stimulating factor.
The revised terms also call for Cytokinetics to assume responsibility for the research, development and commercialization of other mitotic kinesins, save for centromere-associated protein E, which is the focus of translational research activities being conducted by GSK and Cytokinetics and development activities being conducted by GSK.
As a result of those changes, Cytokinetics revised its guidance for the fiscal year, forecasting research and development expenses to range between $52 million and $56 million, as well as general and administrative expenses between $16 million and $19 million.