Home About Us Pipeline Expanded Access Investors & Media Contact Us BPDCN HomePipeline WATCH THE MOA ELZONRISTM (TAGRAXOFUSP, SL-401) ELZONRISTM (tagraxofusp, SL-401) — ELZONRIS is a novel targeted therapy directed to the interleukin-3 (IL-3) receptor-α (CD123), a target present on a wide range of malignancies. ELZONRIS was approved by the US Food and Drug Administration (FDA) on December 21, 2018, for the treatment of adult and pediatric patients, 2 years and older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). In January 2019, a marketing authorization application (MAA) for ELZONRIS for the treatment of patients with BPDCN was submitted to the EMA. Previously, the EMA granted the MAA accelerated assessment status. In parallel, Stemline is evaluating ELZONRIS in clinical trials in additional indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and others. CD123 BACKGROUND CD123 is expressed on multiple malignancies including BPDCN, AML, certain myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), B-cell acute lymphoid leukemia (B-ALL), hairy cell leukemia, and Hodgkin’s and certain non-Hodgkin’s lymphomas. In addition to expression on tumor bulk, CD123 expression has been reported on the cancer stem cells (CSCs), of certain hematologic cancers including AML, CML, MDS, and potentially T-cell ALL. In addition, elevated CD123 expression has been correlated with poor prognosis in certain hematologic cancers. Notably, neoplastic CD123+ pDCs, which are the cell of origin for BPDCN, have been found in a number of myeloid neoplasms, including CMML, MDS, and AML, and are associated with poor prognosis. Additionally, neoplastic CD123+ pDCs have also been reported in the microenvironment of certain tumors including multiple myeloma, CMML and other MPNs, and in certain solid tumors where they could play a tumor-promoting role. Preclinical experiments in multiple myeloma have shown these pDCs to have a tumor-promoting effect. Neoplastic CD123+ pDCs have also been implicated in the pathogenesis of certain autoimmune diseases, including scleroderma and cutaneous lupus, and are under evaluation as a potential therapeutic target for these conditions. SL-701 SL-701 is an immunotherapy designed to direct the immune system to attack targets present on certain malignancies including brain cancer. SL-701 comprises 3 short synthetic peptides that correspond to epitopes of targets including IL-13Rα2, EphA2, and survivin; 2 of these synthetic peptides (IL-13Rα2 and survivin) are mutant and believed to enhance immune activity. A multicenter Phase 2 trial of SL-701 in adult patients with second-line glioblastoma multiforme (GBM) has been completed, and data suggest that SL-701 is generating a target-specific CD8+ T-cell response, which may be translating into improved clinical outcomes, including improved overall survival, in a subset of patients. Given the safety and efficacy data generated to date with SL-701 and bevacizumab in second-line GBM, an indication of unmet need, we are considering next steps including leveraging these results and the potential immune-related data in registration-directed trial designs. SL-701 Background and Mechanism of Action SL-701 is an off-the-shelf, systemically delivered (subcutaneous) immunotherapy designed to target IL-13R⍺2, EphA2, and survivin, which overexpressed on glioblastoma (GBM). Composed of short, synthetic peptides, some mutated, SL-701 appears to generate an antigen-specific CD8+ T-cell response when coadministered with immunostimulants. SL-801 SL-801 is a structurally novel, oral, small molecule, reversible inhibitor of exportin-1 (XPO1), a nuclear transport protein implicated in both solid tumors and hematologic malignancies. SL-801 has demonstrated preclinical in vitro and in vivo antitumor activity against a wide array of solid and hematologic cancers. SL-801’s potential ability to reversibly bind XPO1 may offer the possibility to mitigate side effects and help optimize the therapeutic index. A multicenter Phase 1 dose escalation trial of single agent SL-801 is currently enrolling patients with advanced solid tumors. XPO1 BACKGROUND XPO1 has been shown to regulate nuclear export of many of the major tumor suppressor proteins and oncogenic cell growth regulators. Overexpression of XPO1 has been reported in many cancer types and is associated with aggressive tumor behavior and poor patient prognosis. Inhibition of XPO1 has been shown to restore tumor suppressor function and proper cell cycle regulation, leading to apoptosis of cancer cells. XPO1 has also been shown to be a clinically validated target in both solid and hematological cancers. SL-801 has demonstrated broad and SL-801 has demonstrated broad and potent preclinical activity in a wide array of solid and hematologic tumors, as well as neurologic disorders, in both in vitro and in vivo xenograft experiments. In a screening against 240 cancer cell lines, SL-801 possessed strong anti-tumor activity, with 50% growth inhibitory values less than 10 nM in 21.3% of cell lines and less than 100 nM in 95.8% of cell lines. As a single agent, SL-801 also significantly prolonged overall survival and inhibited tumor growth in several mouse xenograft models of human multiple myeloma, as well as in xenograft models of acute lymphoblastic leukemia, non-small cell lung cancer, and prostate carcinoma, in well-tolerated single-dose or multidose regimens. SL-801’s ability to reversibly bind XPO1 may offer the potential to improve the therapeutic index in humans VISIT BPDCNINFO.COM A RESOURCE FOR PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM Find out about the latest research, news, and clinical trials. About Us Management Business Development Pipeline Clinical Trials Scientific Presentations Investors & Media News & Events Contact Us BPDCN © 2021 – Stemline Therapeutics, Inc. All rights reserved | Privacy & Terms of Use | CCPA Policy | Cookie Policy Stemline Therapeutics is a society of the Menarini Group