Calistoga Pharmaceuticals has come a long way in one year.
The Seattle-based biotech company made its first ripple on the national scene last year at the American Society of Clinical Oncology (ASCO), when it showed its novel drug for blood cancers caused tumor shrinkage in half of the first dozen patients tested. This year at the same confab, researchers led by Richard Furman of Weill Cornell Medical College in New York, had a much meatier set of results to show off. The early hint of effectiveness—and it was really just a hint last year—has much more solid confirmation now that 106 patients have been studied, and some longer-term follow up data is trickling in.
About 57 percent of patients with a slow-growing form of non-Hodgkin’s lymphoma had their tumors shrink by half or more, two-thirds with mantle cell lymphoma did that well, while 30 percent of patients with chronic lymphocytic leukemia had that response, researchers said yesterday at ASCO. Still, like any drug, this one has side effects. Researchers saw increasing rates of certain liver enzymes in the blood of patients who took high doses of the drug, which can be a warning sign of liver damage, something the FDA often monitors carefully. Calistoga says the side effect didn’t cause any observable liver symptoms in patients, and the enzyme levels returned to normal after doctors reduced the doses. (For a look at the detailed presentation slides, click here.)
“We have a clear signal now in terms of efficacy,” says Calistoga CEO Carol Gallagher.
Calistoga bears watching as one of the most promising privately held biotech companies in the Northwest. It raised $30 million in venture capital just a few weeks before it released the first glimpse of data at ASCO last year. The company is pursuing one of the prime targets in cancer biology today—the PI3 kinase pathway. Researchers are excited about this pathway because it is thought to control critical cell processes like proliferation, migration, and cell survival. When these normal functions get flipped into an overactive mode, it’s a hallmark of cancer cells spiraling out of control, or an immune system gone wild so that it attacks healthy tissue.
Calistoga was founded in 2006 with some intellectual property from Icos to develop drugs against the PI3K enzyme. There are plenty of competitors in this hot field—including GlaxoSmithKline, Novartis, Roche, Exelixis, Oncothyreon, and Intellikine. Many of the rivals make drugs that hit a broad cross-section of PI3K enzymes, and Calistoga claims to be different because its lead candidate is made to hit a specific subtype of PI3 kinase, known as the delta isoform. The hope is that Calistoga’s lead drug, CAL-101, may have a better profile for blood cancers that express the delta isoform, and that it may have milder side effects, a useful feature if Calistoga wants to treat chronic conditions like inflammatory diseases.
The last time Calistoga talked publicly about CAL-101 was back in December at the American Society of Hematology meeting, when it had results from 57 patients. The easiest way to look at this updated data from 106 patients is through a chart, so that’s what I’m providing below. But a little background is required first. This study enrolled a wide variety of patients with blood cancers. More than half of them had relapsed or didn’t respond any more to existing therapies. Without receiving any other combination treatments, people in the study took CAL-101, a twice-daily oral pill, for a 28-day cycle of therapy, for as many as 12 cycles. Here is how patients responded in each group.
| Disease | Responders | Percentage |
| Slow-growing “indolent” non-Hodgkin’s lymphoma | 13/23 | 57 percent |
| Mantle cell lymphoma | 8/12 | 67 percent |
| Chronic lymphocytic leukemia | 10/33 | 30 percent |
| Acute myeloid leukemia | 0/11 | 0 percent |
| Multiple myeloma | 0/11 | 0 percent |
Response rates like that beg an obvious question: How long did the effect last? Cancer is
