On December 10, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported data from ELZONRIS (tagraxofusp) Phase 1/2 clinical trials in myelofibrosis (oral presentation) and multiple myeloma, at the 2019 ASH (Free ASH Whitepaper) annual meeting (Press release, Stemline Therapeutics, DEC 10, 2019, View Source [SID1234552195]). The presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab. Highlights of results are presented below.

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Myelofibrosis: Clinical Trial of ELZONRIS in Patients with Intermediate or High-Risk, Relapsed/Refractory Myelofibrosis (MF) – Oral presentation

ELZONRIS demonstrated efficacy (spleen size reductions and total symptom score [TSS] reductions) with a predictable and manageable safety profile, including in patients with poor prognostic factors, such as thrombocytopenia, CMML-type features/monocytosis, and clonal evolution
45% (9/20) of patients had symptom burden reduction, including 3 with symptom response per IWG-MRT 2013 MF response criteria
53% (8/15) of patients with baseline splenomegaly >= 5cm experienced a spleen size reduction; 20% (3/15) had a reduction >35% (specifically 100%, 47% and 46% reductions)
° 100% (5/5) of patients with CMML-type features/monocytosis experienced a spleen size reduction, and 40% (2/5) of these patients had a reduction >35%
° 64% (7/11) of patients with thrombocytopenia (platelet count < 100×109/L) experienced a spleen size reduction, and 18% (2/11) had a reduction >35%; 60% (3/5) of patients with thrombocytopenia (platelet count < 50×109/L) experienced a spleen size reduction, and 20% (1/5) had a reduction >35%

Most common treatment related adverse events (TRAEs) include alanine aminotransferase increase, headache, hypoalbuminemia (all 17%), anemia, and thrombocytopenia (both 14%)
° There was one case of capillary leak syndrome (CLS), which was grade 3
43% overall survival (OS) at 18 months; 29% OS at 2 years
Next Steps

Expansion of Phase 2 trial to include additional sites is underway
Patient enrollment and follow up continues to inform design of potential registration-directed trial of ELZONRIS in patients with relapsed/refractory MF, including poor prognosis patients with:
° Thrombocytopenia, and/or
° Monocytosis (CD123-overexpressed subsets)
Other areas of evaluation in MF

An additional ASH (Free ASH Whitepaper) presentation demonstrated that ELZONRIS, either alone or in combination with ruxolitinib, had preclinical activity against primary MF patient samples, including those in accelerated phase and with high molecular risk profiles where current therapeutic options beyond ruxolitinib are limited and CD123 expression is evident. These data support further evaluation of tagraxofusp in MF, not only as single agent but potentially in combination with Jak inhibitors.
Multiple Myeloma: Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Multiple Myeloma (MM)

ELZONRIS, in combination with pomalidomide (POM) and dexamethasone (DEX), demonstrated activity and a predictable and manageable safety profile in heavily pretreated patients with relapsed/refractory MM
56% of patients (5/9) who received ELZONRIS in combination with POM+DEX had partial responses (PRs)
° Notably, these patients also had decreases in their plasmacytoid dendritic cells (pDCs), a cell type implicated in myeloma growth and aggressiveness, and the cell of origin of blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Given these clinical data, ELZONRIS may offer a novel mechanism of action and future therapeutic option for patients with MM
Next Steps

Given these encouraging early results, potential avenues for further ELZONRIS development are being assessed, including evaluating additional patients with this and/or potentially other regimens including in combination with daratumumab or novel agents such as XPO1 inhibitors. Moreover, the clinical knockdown of pDCs in MM patients may also be relevant with respect to other diseases, such as chronic myelomonocytic leukemia (CMML), MF and certain acute myeloid leukemia (AML) patient subsets, where pDCs have been similarly implicated in the aggressiveness of these malignancies.
About ELZONRIS
ELZONRIS (tagraxofusp), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.