Menarini Ricerche Announces SEL24/MEN1703 Pharmacodynamic Data from the Dose Escalation Part of DIAMOND-01 Trial

- SEL24/MEN1703 is being Evaluated for the Treatment of Acute Myeloid Leukemia (AML)

- Poster Accepted for Presentation at the 62^nd American Society of Hematology (ASH) Annual Meeting

POMEZIA, Italy and ROME, Dec. 1, 2020 /PRNewswire/ -- Menarini Ricerche, the R&D division of the Menarini Group, reported today the positive results of the pharmacodynamic assay demonstrating target engagement in the dose escalation part of the DIAMOND-01 trial (CLI24-001; clinicaltrials.gov identifier NCT03008187), a study investigating SEL24/MEN1703, a first-in-class, orally available, dual PIM/FLT3 inhibitor as single agent in Acute Myeloid Leukemia (AML).

The poster entitled "SEL24/MEN1703 provides PIM/FLT3 Downstream Pathway Inhibition in Acute Myeloid Leukemia (AML) Blast Cells: Results of the Pharmacodynamic (PD) Assay in the Dose Escalation Part of First-in-Human DIAMOND Trial" will be presented at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition, which will take place virtually on December 5-8.

"We are pleased with the preliminary, positive results observed with SEL24/MEN1703, a PIM/FLT3 inhibitor under investigation for the treatment of AML. As outlined in our ASH poster presentation, the dose escalation phase of the DIAMOND-01 trial showed that SEL24/MEN1703 has a manageable safety profile and results in a meaningful target engagement in peripheral blood and bone marrow blast cells from patients treated with SEL24/MEN1703," said Andrea Pellacani, General Manager of Menarini Ricerche. "We look forward to continuing our investigation of SEL24/MEN1703 as a potential new treatment for this aggressive and hard-to-treat cancer, as part of our commitment to develop effective innovative therapies that can make a difference in the lives of cancer patients."

DIAMOND-01 is the First-in-Human, Phase I/II dose escalation and cohort expansion trial of SEL24/MEN1703, in-licensed by Menarini from Ryvu Therapeutics, in AML. The study has completed the dose escalation part showing a manageable safety profile up to the recommended dose of 125 mg/day, with initial evidence of anti-leukemic activity in a single agent setting.

The objective of the pharmacodynamic assessment was to investigate the degree of target engagement achieved at different doses of SEL24/MEN1703, by measuring the phosphorylation of S6 (pS6), a downstream effector of the PIM/FLT3 signaling pathway. In addition, the correlation between pS6 levels and the anti-leukemic effect of SEL24/MEN1703 was assessed in samples collected from patients enrolled in the dose escalation part of the DIAMOND-01 trial. The quantitative assessment of pS6 at a single-cell level was performed both on peripheral blood (PB) and bone marrow (BM) blast cells samples.

The results of this assay confirmed that meaningful target engagement was achieved, both in PB and BM blast cells, in patients treated with SEL24/MEN1703 at 100 mg/day (one dose level below the recommended dose) and at 125 mg/day. Moreover, preliminary data suggest that the PIM/FLT3 pathway inhibition might be associated with blast count reduction, particularly in those patients showing high phosphorylation of S6 at baseline.

We will continue to measure target engagement with this assay in the cohort expansion part of the DIAMOND-01 trial, which is currently recruiting patients with relapsed or refractory AML in both the EU and the US.

About MEN1703

SEL24/MEN1703 is a first-in-class, orally available, dual PIM/FLT3 inhibitor in-licensed by Menarini from Ryvu Therapeutics. It is an investigational compound, not approved for use by regulatory authorities, currently being evaluated in the DIAMOND-01 trial (CLI24-001; clinicaltrials.gov identifier NCT03008187) for the treatment of Acute Myeloid Leukemia.

About Menarini

Menarini Ricerche is the Menarini Group's division dedicated to R&D, with a strong commitment to oncology research and development, as well as an active engagement in the infectious disease area, being involved in the fight against the antimicrobial resistance threat, a rising global concern.

As part of its commitment to oncology, Menarini's pipeline includes five investigational compounds for the treatment of a variety of hematological and/or solid tumors: two biologics (the monoclonal antibody anti-CD157 MEN1112/OBT357, and toxin-conjugated anti-CD205 antibody MEN1309/OBT076), and three small molecules (the dual PIM and FLT3 kinase inhibitor SEL24/MEN1703, the PI3K inhibitor MEN1611, and the inhibitor of class I, II, and IV histone deacetylase, Pracinostat). The acquisition of Stemline Therapeutics, a New York-based biopharmaceutical company, strengthened Menarini's oncology portfolio with the addition of both commercial and clinical-stage assets. These assests include ELZONRIS^Ò (tagraxofusp), a targeted therapy directed to CD123, FDA-approved and commercially available in the U.S. for the treatment of adult and pediatric patients, two years and older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Menarini has also entered into a license agreement with Radius Health for the development and commercialization of Elacestrant, an oral SERD in late stage Phase 3 development as a potential hormonal treatment for breast cancer. Through the work of Menarini Silicon Biosystems, Menarini is also developing advanced technologies and products to study rare cells with single-cell precision.

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of €3.793 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, gastroenterology, pneumology, infectious diseases, diabetology, inflammation, and analgesia. With 17 production sites and 10 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit www.menarini.com

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