On December 6, 2018 Stemline Therapeutics, Inc. (Nasdaq: STML), a biopharmaceutical company focused on the development and potential commercialization of novel oncology therapeutics, reported that updated data from multiple ELZONRISTM (tagraxofusp; SL-401) clinical trials at the 2018 ASH (Free ASH Whitepaper) Annual Meeting (Press release, Stemline Therapeutics, DEC 6, 2018, View Source [SID1234531924]). Presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.

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Key Outcomes from Pivotal Trial of ELZONRIS in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Across all 3 stages, 42 patients received ELZONRIS (12 ug/kg/day)
• In first-line patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 90% (26/29) overall response rate (ORR)
– 72% (21/29) rate of CR + CRc (complete response + clinical CR [CR with residual skin abnormality])
– 45% (13/29) of patients were bridged to stem cell transplant (SCT)
• In relapsed/refractory patients with BPDCN, ELZONRIS (12 ug/kg/day)
– 69% (9/13) ORR
– 38% (5/13) CR + CRc + CRi rate
– 1 patient was bridged to SCT
• Median overall survival (OS) was not yet reached in first-line patients treated with ELZONRIS at 12 ug/kg/day across all stages. Median follow up time is 23.0 months (range of 0.2 – 41+ months)
• Most common treatment-related adverse events (TRAEs) in all patients treated across all trials at 12 ug/kg/day dose (N=148) were: alanine aminotransferase increase (43.9%), aspartate aminotransferase increase (43.9%), hypoalbuminemia (43.9%), and thrombocytopenia (26.4%). TRAEs included capillary leak syndrome (CLS) (16.9%) which was grade 5 in 1.5% (3/202) of patients across all trials and doses and 0.6% (1/166) of patients across all trials at 12 ug/kg/day; a myocardial infarction, grade 5, occurred in a patient (12 ug/kg/day) with grade 4 CLS, as previously reported.

Stage 3 pivotal cohort (13 first-line BPDCN patients treated with SL-401 at 12 ug/kg/day):
• Met its primary endpoint with a 54% (7/13) CR + CRc rate (95% CI: 25.1, 80.8)
• 77% (10/13) ORR
• 46% (6/13) of patients were bridged to SCT
In the U.S., the ELZONRIS biologics license application (BLA) is under Priority Review, with a February 21, 2019 PDUFA action date

In the E.U., the European Medicines Agency (EMA) has granted accelerated assessment to the planned Marketing Authorization Application (MAA), which is expected to be submitted in the first quarter of 2019
Key Outcomes from Ongoing Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)

ELZONRIS demonstrated efficacy (spleen and bone marrow responses), with a manageable safety profile, in patients with relapsed/refractory CMML, an area of unmet medical need

100% of evaluable patients had reduction in baseline splenomegaly
– 80% had reduction by ≥50%
– 67% with baseline spleen size ≥5cm had reduction by ≥50%

3 bone marrow complete responses (BMCRs)

1 patient bridged to stem cell transplant in remission on ELZONRIS

Most common TRAEs include hypoalbuminemia (35%), thrombocytopenia (35%), nausea (30%) and vomiting (30%). Most common TRAEs, grade 3+, include thrombocytopenia (35%) and nausea (5%). CLS was reported in 15% of patients, with no cases of grade 3 or higher observed

Splenomegaly has historically been associated with serious sequelae including early satiety and intractable pain, as well as poor transplant outcomes and a higher propensity for AML transformation

Targeting the proliferative component of CMML, namely alleviation of splenomegaly, could result in meaningful clinical benefit and address a key unmet medical need
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on the encouraging results seen in this trial, a registrational trial design, or pivotal cohort, is being designed
Key Outcomes from Ongoing Trial of ELZONRIS in Patients with Relapsed/Refractory Myelofibrosis

ELZONRIS monotherapy demonstrated efficacy (improvements in splenomegaly), with a manageable safety profile, in patients with relapsed/refractory MF, an area of unmet medical need; Patient enrollment and follow up continues

100% of evaluable patients with monocytosis and baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 80% had reduction by ≥29%; 40% had reduction by ≥45%
– Historically, monocytosis has been associated with poor prognosis in certain MF patients

57% of evaluable patients, with baseline spleen size ≥5cm, had reduction in baseline splenomegaly
– 43% had reduction by ≥29%; 21% had reduction by ≥45%

6 patients with spleen response had treatment duration of 6+ months; 5 patients ongoing
– 5 patients with baseline thrombocytopenia (platelet count <100K) had treatment duration of 6+ months; 4 ongoing
– 3 patients with baseline monocytosis (>1×109/L) had treatment duration of 8+ months; 2 patients ongoing

Initial quality of life (QOL) assessments appear promising; full symptom score analyses are ongoing

Most common TRAEs include headache and hypoalbuminemia (each 22%), and alanine aminotransferase increased and thrombocytopenia (each 17%). The most common TRAE, grade 3+, was thrombocytopenia (8%). There was one case of CLS, which was grade 3.
Next Steps

Patient enrollment and follow up continues, and additional updates are planned in 2019

Based on these encouraging results, next steps are being evaluated including single agent, combination, and registration-directed trials in patients with relapsed/refractory MF, including in poor-prognosis MF patients with monocytosis, an area of unmet medical need
Ivan Bergstein, M.D., CEO of Stemline, commented "The ELZONRIS clinical presentations showcased at ASH (Free ASH Whitepaper) demonstrate a broad clinical potential in a wide range of malignancies. In particular, we believe that our data in relapsed/refractory CMML and MF provides important clinical proof-of-concept in two indications with unmet medical need, and underscores just two of the many potential expansion opportunities that targeting CD123 offers. At ASH (Free ASH Whitepaper), we continued to ramp-up our disease awareness campaign for BPDCN ahead of the upcoming FDA decision on the ELZONRIS BLA. Also, our sales force is prepared and poised to launch ELZONRIS, should approval be obtained. In parallel, our clinical development team is moving forward with plans to expand efforts, including initiating one or more registration-directed trials in indications beyond BPDN, while also continuing to pursue novel entry points in CD123+ acute myeloid leukemia (AML) and other malignancies."

About BPDCN
To learn more about BPDCN, please visit the disease awareness website at www.bpdcninfo.com.