West Coast Editor

Retooling the kinesin-inhibitor deal with GlaxoSmithKline plc in a way that could lead to better financials related to one of the compounds, Cytokinetics Inc. is halting part of a Phase II trial with another, due to unsatisfying interim results.

The company's stock (NASDAQ:CYTK) closed Wednesday at $7.96, down 46 cents, after trading as low as $7.

First, the less-than-good news: In a Phase II trial testing ispinesib (formerly known as SB-715992) against non-small-cell lung cancer, platinum-refractory patients did not show enough benefit in a planned interim analysis for them to proceed with more treatment.

"It's definitely a high hurdle," said Robert Blum, chief business officer of South San Francisco-based Cytokinetics, adding that the outcome was "not a huge surprise, but a bit of a disappointment." A second arm of the study, enrolling platinum-sensitive patients, goes on, with the interim look at results due by the end of this year.

In a Phase II trial of ispinesib for locally advanced or metastatic breast cancer, though, the compound turned up sufficient clinical activity to proceed to the next stage of the study.

The breast-cancer trial pits the drug against breast cancer as a second- or third-line therapy for patients whose disease has recurred or progressed despite treatment with anthracyclines and taxanes, and the trial now is expected to proceed to full enrollment of 55 evaluable patients.

Designed to require at least three confirmed partial or complete responses out of 30 evaluable patients in order to proceed to the second stage, the study's primary endpoint is response rate as determined by RECIST criteria. The acronym stands for Response Evaluation Criteria in Solid Tumors, a method that deploys X-ray, CT scans and MRI.

Though Wall Street took the mixed NSCLC news poorly, seeing the "glass half empty rather than the glass half full," Blum is optimistic about the second arm of that study as well as the final data from the breast-cancer trial.

"It would be unprecedented that [the drug would be active] in breast and not other tumor types, given that all cancer cells that are dividing make use of this target enzyme for their mechanics," he said.

The best overall breast cancer outcomes seen so far have been partial responses observed in required three patients, and all patients enrolled have had metastatic disease. Detailed interim data are expected to be presented at the 28th San Antonio Breast Cancer Symposium in December.

New York-based Credit Suisse First Boston downgraded Cytokinetics from "neutral" to "underperform" Wednesday, but analyst Gregory Wade with Pacific Growth Equities in San Francisco kept his "overweight" rating on Cytokinetics' stock and noted in a research report that the good news with ispinesib in breast cancer "provides the first clinical validation of [the company's] oncology franchise."

In all, nine Phase II trials are testing ispinesib.

Cytokinetics and London-based partner GSK are expanding their 2001 deal in relation to the second kinesin inhibitor, SB-743921, a distinct small molecule intended to modulate cell proliferation and kill cancer cells by blocking the spindle protein. (See BioWorld Today, June 26, 2001.)

Under the terms of the new arrangement, Cytokinetics will lead and fund development activities to explore SB-743921 against non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma, subject to GSK's option to take responsibility for those efforts during a "defined period" that Blum would not specify.

"This is a situation of us stepping up to do more as opposed to GSK stepping back to do less," Blum told BioWorld Today. The renegotiated deal has been in the works for "many months," he said, whereas the mixed interim data in the NSCLC became available much more recently.

Cytokinetics' development work will be conducted in parallel with GSK's for SB-743921 in other indications and for ispinesib, and the duo will speed up their formation of a joint development committee that will oversee the efforts.

Along with payments potentially due from GSK under the original terms of the collaboration, Cytokinetics could get more pre-commercialization cash if certain milestones are met. Blum was not specific about those, either, but noted that Cytokinetics has not revised its financial guidance for 2005. The firm had $95 million in cash and cash equivalents as of June 30, enough to operate for more than 20 months.

There's more in the Cytokinetics hopper, including a Phase I stimulator of the cardiac myosin motor protein, designed to treat acute heart failure intravenously and which might work orally for chronic heart failure.

"Ideally, you want a drug that can increase the efficiency of contractility without taxing [the heart] by increasing oxygen demand and heart rate," Blum said. The drug worked in dogs, and "dog models in heart failure are predictive," he said.

The heart failure compound is not partnered and Cytokinetics' goal is to commercialize the drug on its own, though results with the I.V. form will determine what's done with an oral version, and "we never say never" to deals, Blum said.

Behind the heart drug is a program exploring smooth muscle inhibitors that might work against hypertension or asthma, he said, and another program experimenting with skeletal muscle could target frailty in geriatrics.

No Comments