Stemline Therapeutics Targets Capacity of Tumors to Adapt and Proliferate

The investigational cancer medications being developed by Stemline Therapeutics attack only a tiny percentage of all tumor cells. But those few cells—the stem cells that resist most treatment and drive tumor growth—may just be the most important ones.

Stemline’s lead compound, a novel biologic therapy called SL-401 that targets the interleukin-3 receptor (IL-3R), has shown significant activity in phase I/IIa testing against a handful of tumor types, including acute myeloid leukemia (AML) and multiple myeloma.

A second Stemline drug candidate, the peptide-based vaccine SL-701 that targets multiple glioma-associated antigen epitopes, has shown significant activity in phase I/IIa testing against pediatric malignant glioma and adult high-grade glioma.

The clinical performance of those experimental medications, combined with the promise of a drug development platform licensed from Cambridge University, helped the Manhattanbased company raise $69 million during its initial public stock offering this May.

Stemline’s technology is complex, but the logic of its approach is simple: Cancers, like their hosts, have stem cells that, while small in number, can divide incredibly quickly and form any kind of cell. These cancer stem cells also tend to survive conventional treatments, such as chemotherapy and radiation, and eventually build the new tumors that cause patients to relapse.

Stemline aims to halt this process with products that kill the stem cells, prevent the formation of new tumors, and vanquish cancer for good. Although the company is years away from bringing drugs to market, it has shown that its compounds can produce significant activity.

In one study, 59 patients with heavily pretreated AML each received a single 5-day course of SL-401. Doses varied (one of the study’s aims was to establish the maximum-tolerated dose) but among patients who received a therapeutically relevant dose, overall survival was more than three times greater than that expected for untreated patients. Two patients experienced durable complete remissions, one lasting 8 months, and the other lasting more than 25 months.

That study, which was presented at the 2013 American Society of Clinical Oncology Annual Meeting, also established that there are effective doses of the medication well below the maximum-tolerated dose, which was 16.6 μg/kg/day (hypoalbuminemia and edema occurred in patients at higher doses).

Smaller clinical studies have demonstrated the activity of SL-401 against other tumor types. For example, among four patients with heavily pretreated blastic plasmacytoid dendritic cell neoplasm who received a single dose of SL-401 as part of the same study, three experienced complete remissions lasting 1 to 5 months.

As for SL-701, its largest trial to date was a phase I/ IIa study on 22 recurrent malignant glioma patients with different tumor types. After an 8-week course of injections, 81% had ≥1 positive immunogenicity assay. Approximately 46% of recurrent glioblastoma patients and 67% of recurrent anaplastic glioma patients had tumor shrinkage or stable disease. One recurrent glioblastoma patient sustained a complete response for >14 months, and two patients achieved a partial response.

Stemline has announced plans for several phase IIb studies.

Stemline Therapeutics Pipeline