On June 6, at the meeting of the American Society of Clinical Oncology (ASCO), a University of Pittsburgh scientist working with New York-based Stemline Therapeutics revealed that two patients in an early trial of the company’s drug had recovered from advanced malignant glioma—a deadly form of brain cancer. Another patient, a 10-year-old girl in a pediatric trial of the drug, saw her tumors shrink more than 50 percent.
Stemline’s presentation was overshadowed by more advanced cancer research presented by the likes of Pfizer and Bristol-Myers Squibb. But for the tiny team at Stemline, the conference—its first ASCO appearance—was still a major milestone for the drug, called SL-701. “We were pretty excited,” says Ivan Bergstein, CEO of Stemline. “They put us in a large amphitheater, and we got a good turnout.”
The crowds likely showed up in force because of a growing interest in the company’s approach, which is to attack cancer stem cells (CSCs)—master cells that are “tumorigenic,” or tumor-forming. Those cells are among the most important targets in the war against the disease. That’s because CSCs tend to resist standard cancer treatments, such as chemotherapy. So even if a patient’s tumor is greatly diminished with chemo, the CSCs within the tumor often survive, causing relapse and ultimately death.
Bergstein, a hematologist and oncologist by training, founded Stemline in 2003. The company developed a technology platform that can isolate CSCs with fluorescent markers, which in turn speeds up the process of screening for compounds that help combat the virulent cells. The technology, called StemScreen, has produced several of Stemline’s clinical candidates. The company’s two most advance projects are SL-701 and a treatment for blood cancers called SL-401, both of which are progressing in the clinic towards the pivotal late-stage trials that will be required for FDA approval.
Stemline’s scientists selected the drugs over other molecules that showed up in the screening process largely because of their “dual effect,” Bergstein says. “They hit the non-stem-cells, as well as the stem cells,” he explains. SL-701, for example, which Stemline licensed from the University of Pittsburgh, is a therapeutic vaccine that mobilizes the immune system by attacking multiple targets on both tumor cells and cancer stem cells. “Our prediction is that the dual effect will make the tumor shrinkage more durable” than it is with standard chemo and radiation, Bergstein says. And though the clinical program is not advanced enough to produce solid survival data, in the early trials, “the population as a whole is living longer,” Bergstein says.
SL-401 is also a dual-acting drug. It targets the interleukin-3 receptor (IL-3R), which is overly abundant in the cancer cells and stem cells of many blood cancers, including acute myeloid leukemia (AML). In two trials of the drug that Stemline presented at the American Society of Hematology meeting in December, the company was able to show a significant survival benefit, including two remissions.
Unlike other experimental treatments for AML, such as that being developed by Stemline’s New Jersey neighbor Cyclacel Therapeutics, SL-401 is not a chemotherapeutic agent. Many chemo treatments affect normal hematopoietic—or blood-forming—stem cells, as well as cancer cells. But the IL-3 receptor that SL-401 targets is not prevalent on those normal stem cells, so it may have much less of a destructive effect on healthy cells than chemo does, Bergstein says.
If all goes well, Stemline could be in Phase 3 trials on both of its lead compounds next year. And it’s moving towards those pivotal trials with a workforce of about a dozen, and just $12.5 million that it raised in a 2007 Series A round from the hedge fund company Pequot Capital Management (now defunct). Stemline is a lean, “virtual company” that relies heavily on its academic collaborators, which over the years have included Memorial Sloan-Kettering Cancer Center in New York, Johns Hopkins, and the University of Texas MD Anderson Cancer Center. “We’ve been very careful in the way we spend our money,” Bergstein says.
Stemline’s executives have started talking to potential funding sources about raising another round, but Bergstein says the company doesn’t yet need to seek out a Big Pharma partner for either lead drug. “Our philosophy is to have the wherewithal to develop these drugs on our own,” he says.
When Bergstein started Stemline, he was a bit of a lone wolf in his pursuit of cancer stem cells, he says. But his career path convinced him it was an area worth exploring. Bergstein completed a fellowship in hematology and medical oncology at New York Presbyterian Hospital-Weill Medical College of Cornell University, where he is still a volunteer faculty member. He later worked as a biopharmaceuticals analyst on Wall Street at Cancer Advisors Inc., which advised investment funds on publicly held oncology companies. “I convinced myself that cancer stem cells were key to attacking the disease,” he says.
Now a number of companies have started exploring CSCs, including biotechs OncoMed of Redwood City, CA, and Boston-based Verastem, as well as a handful of Big Pharma firms that are “starting to dabble internally,” Bergstein says.
All that fascination with CSCs can only help Stemline, Bergstein believes, especially as the company gears up to raise more capital. “The more activity the better,” he says. “CSC research is reaching a tipping point.”