Menarini Group and Nippon Shinyaku Enter into an Exclusive License Agreement to Develop and Commercialize ELZONRIS® (Tagraxofusp) in Japan

• Menarini advances the global roll out of Elzonris and underscores its commitment to delivering innovative medicines around the world
• Partnership with Nippon Shinyaku allows Menarini to start building a footprint in Japan

FLORENCE, ITALY March 29^th, 2021 – The Menarini Group announced today that it has entered into an exclusive license agreement for the development and commercialization of ELZONRIS® (tagraxofusp) in the territory of Japan with Nippon Shinyaku Co., Ltd. ELZONRIS is approved for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) by the U.S. Food and Drug Administration and the European Medicines Agency.

BPDCN is a rare, aggressive hematologic malignancy with historically poor outcomes. ELZONRIS (tagraxofusp) is the first approved treatment for patients with BPDCN, and the first approved CD123-targeted therapy, in both the United States and Europe.

“Partnering with Nippon Shinyaku marks another important step forward in our effort to meet the needs of patients with difficult-to-treat diseases and underscores our commitment to delivering innovative medicines for people around the globe,” commented Elcin Barker Ergun, CEO of the Menarini Group. “Patients with BPDCN have limited treatment options and we are excited to be collaborating closely with Nippon Shinyaku to make ELZONRIS (tagraxofusp) available to patients in Japan.”

About ELZONRIS^® in the European Union

ELZONRIS® (tagraxofusp) is indicated as monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). ELZONRIS should be administered under the supervision of a physician experienced in the use of anti-cancer agents.

About ELZONRIS^® in the USA

ELZONRIS® (tagraxofusp), a targeted therapy directed to CD123, 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 BPDCN. For full prescribing information in the U.S., visit www.ELZONRIS.com.

ELZONRIS is also being evaluated in additional clinical trials in other indications, including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and others are planned.

About BPDCN

BPDCN, formerly blastic NK-cell lymphoma, is an aggressive hematologic malignancy, often with cutaneous manifestations, with historically poor outcomes. 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. The World Health Organization (WHO) termed this disease “BPDCN” in 2008; previous names included blastic NK cell lymphoma and agranular CD4+/CD56+ hematodermic neoplasm. 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 malignancies 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 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+ cells have been detected in the tumor microenvironment of several solid tumors as well as in certain autoimmune disorders including cutaneous lupus and scleroderma.

Important Safety Information from EU SmPC

Warnings and precautions

• Capillary leak syndrome (CLS), including life-threatening and fatal cases have been reported with most events occurred during the first five days of the first cycle of treatment. Before initiating therapy, it should be ensured that patients have adequate cardiac function and serum albumin ≥ 3.2 g/dL. During treatment, serum albumin levels should be monitored prior to the initiation of each dose, or more often as clinically indicated. Additionally, patients should be assessed for other signs/symptoms of CLS.Patients should be made aware of identifying CLS symptoms and when to seek immediate medical attention. Intravenous albumin supplementation and dosing interruptions may be required.
• Severe hypersensitivity reactions have been reported with ELZONRIS.
• Thrombocytopenia and neutropenia have been reported in patients treated with ELZONRIS monotherapy.The majority of events were reported in cycle 1 and cycle 2 of treatment, were not dose-limiting and did not recur in subsequent cycles.

• ELZONRIS can cause tumour lysis syndrome (TLS).
• Treatment with ELZONRIS has been associated with elevations in liver enzymes. Acute hepatic failure and liver encephalopathy has been reported in a patient treated with ELZONRIS at a higher dose (16 mcg/kg).

Summary of the Safety Profile

• The most serious adverse reaction that may occur during ELZONRIS treatment is CLS which was reported in 18% of patients with a median time to onset of CLS of 6 days.
• Adverse reactions occurring in ≥ 20% of patients treated with ELZONRIS were hypoalbuminemia, increased transaminases, thrombocytopenia, nausea, fatigue and pyrexia.
• Adverse reactions grade 3 and above according to the Common Terminology Criteria for Adverse events (CTCAE) and occurring in > 5% of patients were increased transaminases, thrombocytopenia and anaemia.

For full prescribing information in Europe please refer to the full SmPC at https://www.ema.europa.eu