The Menarini Group products

TAGRAXOFUSP is a novel targeted therapy directed to the IL-3 receptor α (CD123), a target present on a wide range of malignancies including Blastic Plasmacytoid Dendritic Nell Neoplasm (BPDCN). It comprises human IL-3 recombinantly fused to a truncated diphtheria toxin (DT) payload engineered such that IL-3 replaces the native DT receptor-binding domain. The IL-3 domain of TAGRAXOFUSP directs the cytotoxic DT payload to cells expressing CD123. Upon internalization, TAGRAXOFUSP irreversibly inhibits protein synthesis and induces apoptosis of the target cell. TAGRAXOFUSP was approved by the U.S. FDA in 2018 for the treatment of adult and pediatric patients, 2 years or older, with BPDCN.

Elacestrant is a selective estrogen receptor degrader (SERD) evaluated for potential use as a once daily oral treatment in patients with estrogen receptor positive (ER+)/HER2- advanced or metastatic breast cancer. Studies completed to date, including the positive results from the EMERALD phase 3 trial, indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. Indeed, Elacestrant has been the first oral SERD to show positive results in a pivotal, phase III trial as a monotherapy versus standard of care for the treatment of ER+/ HER2- advanced or metastatic breast cancer.

NEXPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor. XPO1 is a nuclear exporter protein that transport from the nucleus to the cytoplasm several proteins, including tumor suppressors, oncogenes, and proteins involved in governing cell growth; it is often overexpressed, and its function mis-regulated in several types of cancers. By inhibiting the XPO1 protein, tumor suppressors proteins buildup in the nucleus of malignant cells and reduce levels of oncogene products which drive cell proliferation. This ultimately leads to cell cycle arrest and death of cancer cells by apoptosis.

SL-901 is an oral small molecule PI3K and DNA-PK inhibitor that has demonstrated activity against PI3K α/δ and PIK3C2 β. SL-901 has shown preclinical activity against a variety of tumor types. A Phase 1 trial in patients with solid tumors is currently enrolling.

MEN1703 is a dual kinase inhibitor targeting PIM (PIM1, PIM2, PIM 3) and FLT3 kinases. FLT3 internal tandem duplication (FLT3-ITD) is one of the most common genetic lesions in acute myeloid leukemia patients (AML) and is associated with a poor prognosis. PIM kinases are thought to be one of the major drivers of the resistance phenotype to FLT3 inhibitors and their inhibition in relapsed samples restores cell sensitivity to FLT3 inhibitors these agents.

MEN1309 is an antibody-drug conjugate (ADC) constituted by a fully human IgG1 antibody conjugated through a cleavable linker to a cytotoxic agent (a maytansin derivative, DM4), responsible for its antitumor activity. The target antigen, CD205, is highly expressed in a wide range of both solid and hematological cancer cells. Once MEN1309 binds its target, the MEN1309/CD205 complex is rapidly internalized in antigen expressing cells where it can exert its cytotoxic activity. MEN1309 is currently being tested as a potential treatment for patients with solid tumors.

Meropenem + Vaborbactam is a fixed dose combination of a carbapenem and a novel boronic acid β-lactamase inhibitor of class A and class C serine β-lactamases, that was specifically developed to inhibit Carbapenem-Resistant Enterobacterales (CRE), including Klebsiella Pneumoniae Carbapenemase (KPC)-producing bacteria. Meropenem exerts bactericidal activity by inhibiting peptidoglycan cell wall synthesis as a result of binding to and inhibition of activity of essential penicillin-binding proteins (PBPs). Vaborbactam forms covalent adduct with β-lactamases and is stable to β-lactamase-mediated hydrolysis. Meropenem / Vaborbactam has been approved in the US and in EU for the treatment of complicated urinary tract infections (cUTI) including acute pyelonephritis. In Europe it has been also approved for the treatment of complicated intra-abdominal infections (cIAI) and hospital-acquired bacterial pneumonia (HABP), such as ventilator associated bacterial pneumonia (VABP).

Oritavancin is a semisynthetic glycopeptidic antibiotic with a long half-life allowing the administration as single dose (1200 mg) by intravenous infusion over 3 hours. It has three mechanisms of action: (i) inhibition of the transglycosylation (polymerization) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors; (ii) inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall; and (iii) disruption of bacterial membrane integrity, leading to depolarization, permeabilization, and rapid cell death. Oritavancin has been approved in the US and in EU for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults.