Innovation & Research

TAGRAXOFUSP is a novel targeted therapy directed to the IL-3 receptor α (CD123), a target present on a wide range of malignancies. 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 is now being investigated for the treatment of Myelofibrosis.

ELCIN Trial is an open-label multicenter Ph 2 trials of Elacestrant in women and men with CDK4/6 inhibitor naïve ER+/HER2- metastatic breast cancer. The study investigates elacestrant as single agent without prior CDK4/6i exposure

SL-701 is an off-the-shelf, systemically delivered (subcutaneous) immunotherapy designed to direct the immune system to attack targets present on certain malignancies, including brain cancer.

SL-701 is composed of three short peptides (IL-13Rα2, EphA2, and Survivin), targeting glioma-associated antigens and designed to generate an antigen specific CD8+ T cell response.
SL-701 is currently being investigated for the treatment of recurrent glioblastoma multiforme.

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.
The spectrum of activity of MEN1703 also warrants the compound investigation in AML patients regardless of FLT3 aberrations.
MEN1703 is being investigated as potential treatment for adult patients with relapsed/refractory AML.

Orphan Drug Designation

MEN1611 is a potent and selective phosphatidylinositol 3-kinase (PI3K) inhibitor with a novel chemical structure targeting the α, β and γ isoforms while sparing the δ, with a novel chemical structure.
The PI3K/Akt pathway regulates various cellular processes such as proliferation, growth, apoptosis and cytoskeletal rearrangement. Various types of cancers are thought to be “addicted” to PI3K/Akt pathway signaling and therefore inhibition of PI3K is a potent therapeutic strategy for fighting cancer.
MEN1611 is being investigated as a potential treatment for patients with PIK3CA-mutated, HER2-positive, advanced or metastatic breast cancer who have failed anti-HER2 based therapy.

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.

FELEZONEXOR (SL-801) is a novel, oral, small-molecule reversible inhibitor of exportin-1 (XPO1), a key nuclear transport protein. XPO1 is overexpressed by many cancers, leading to mislocalization of key tumor suppressors and growth-regulatory proteins in the cytoplasm. FELEZONEXOR is currently being tested as a potential treatment for patients with solid tumors.

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.

ELCIN Trial is an open-label multicenter Ph 2 trials of Elacestrant in women and men with CDK4/6 inhibitor naïve ER+/HER2- metastatic breast cancer. The study investigates elacestrant as single agent without prior CDK4/6i exposure

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.

Important Safety Information

Breakthrough Therapy Designation and Orphan Drug Designation

In Europe, on January 2021 TAGRAXOFUSP was approved by the EMA as monotherapy for the first-line treatment of adult patients with BPDCN.

Important Safety Information

Orphan Drug Designation

MECHANISM OF ACTION

MEN1611 is a potent and selective phosphatidylinositol 3-kinase (PI3K) inhibitor with a novel chemical structure targeting the α, β and γ isoforms while sparing the δ, with a novel chemical structure.
The PI3K/Akt pathway regulates various cellular processes such as proliferation, growth, apoptosis and cytoskeletal rearrangement. Various types of cancers are thought to be “addicted” to PI3K/Akt pathway signaling and therefore inhibition of PI3K is a potent therapeutic strategy for fighting cancer.
MEN1611 is being investigated as a potential treatment for patients with PIK3CA-mutated, HER2-positive, advanced or metastatic breast cancer who have failed anti-HER2 based therapy.

SL-701 is an off-the-shelf, systemically delivered (subcutaneous) immunotherapy designed to direct the immune system to attack targets present on certain malignancies, including brain cancer.

SL-701 is composed of three short peptides (IL-13Rα2, EphA2, and Survivin), targeting glioma-associated antigens and designed to generate an antigen specific CD8+ T cell response.
SL-701 is currently being investigated for the treatment of recurrent glioblastoma multiforme.

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.
The spectrum of activity of MEN1703 also warrants the compound investigation in AML patients regardless of FLT3 aberrations.
MEN1703 is being investigated as potential treatment for adult patients with relapsed/refractory AML.

Orphan Drug Designation

TAGRAXOFUSP is a novel targeted therapy directed to the IL-3 receptor α (CD123), a target present on a wide range of malignancies. 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 is now being investigated for the treatment of chronic myelomonocytic leukemia.

TAGRAXOFUSP is a novel targeted therapy directed to the IL-3 receptor α (CD123), a target present on a wide range of malignancies. 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 is now being investigated for the treatment of Myelofibrosis.

MEN1611 is a potent and selective phosphatidylinositol 3-kinase (PI3K) inhibitor with a novel chemical structure targeting the α, β and γ isoforms while sparing the δ, with a novel chemical structure. The PI3K/Akt pathway regulates various cellular processes such as proliferation, growth, apoptosis and cytoskeletal rearrangement. Various types of cancers are thought to be “addicted” to PI3K/Akt pathway signaling and therefore inhibition of PI3K is a potent therapeutic strategy for fighting cancer.
MEN1611 is being investigated as a potential treatment for patients with PIK3CA mutated, K-RAS, N-RAS and B-RAF wild-type metastatic colorectal cancer, failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.

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.

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.

Delafloxacin is an anionic fluoroquinolone (FQ), with improved characteristics and safety profile in comparison to other FQs It acts through a balanced inhibition of bacterial topoisomerase IV and DNA gyrase (topoisomerase II), enzymes required for bacterial DNA replication, transcription, repair, and recombination. Delafloxacin has been approved in the US for the treatment of the Community Acquired Bacterial Pneumonia (CABP). On April 2021, Delafloxacin has been approved in EU for the for the treatment of CABP.

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. Menarini is currently working on the development of a new Oritavancin formulation consisting in 1 vial to favor the reconstitution of the medical solution and to be administered in shorter times.

New formulation

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.

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. Menarini is currently working on the development of a new Oritavancin formulation consisting in 1 vial to favor the reconstitution of the medical solution and to be administered in shorter times.

New formulation

Delafloxacin is an anionic fluoroquinolone (FQ), with improved characteristics and safety profile in comparison to other FQs It acts through a balanced inhibition of bacterial topoisomerase IV and DNA gyrase (topoisomerase II), enzymes required for bacterial DNA replication, transcription, repair, and recombination. Delafloxacin has been approved in the US for the treatment of the Community Acquired Bacterial Pneumonia (CABP). On April 2021, Delafloxacin has been approved in EU for the for the treatment of CABP.