dapolsertib (MEN1703) / Menarini, Ryvu Therap - LARVOL DELTA

An open-label, Phase 2 study of dapolsertib (MEN1703, SEL24) as monotherapy and in combination with glofitamab in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (ASH 2025) - P1/2, P2 | "Although CAR T-cell therapies (e.g. axicabtageneciloleucel, tisagenlecleucel, lisocabtagene maraleucel) have improved outcomes, access remains limiteddue to logistical and disease-related constraints (Locke et al...More recently, bispecificCD20xCD3 antibodies such as epcoritamab and glofitamab have shown clinical activity in the R/R settingafter ≥2 prior lines, with complete response (CR) rates of ~40% (Dickinson et al...Notably,dapolsertib demonstrated synergy with anti-CD20 antibody, rituximab, providing a rationale forcombination strategies (Szydłowski et al...Keyendpoints include incidence of adverse events, overall/complete response rates, and duration ofresponse. As of July 11, 2025, Part 1 is enrolling in France, Poland, Spain and the UK with additional sitesactivation ongoing."

Clinical • Combination therapy • IO biomarker • Monotherapy • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • BCL6 • FLT3 • PIM1

In silico approaches unveil the mechanism of action of Eclipta prostrata against acute myeloid leukemia. (PubMed, Sci Rep) - "Post-molecular dynamics simulation MM-GBSA analysis further confirmed these interactions, with binding free energies for FLT3: Kaempferol (-73.75 kcal/mol), Apigenin (-68.76 kcal/mol), Pacritinib (-51.27 kcal/mol); and for PIM1: Tricetin (-64.28 kcal/mol), Diosmetin (-52.2 kcal/mol), SEL24 (-53.38 kcal/mol). FLT3 and MPO were identified as specific diagnostic and prognostic biomarkers for AML. This comprehensive in-silico analysis revealed promising therapeutic compounds from E. prostrata targeting FLT3 and PIM1, along with novel biomarker potentials of FLT3 and MPO for improved AML diagnosis and prognosis, subject to further experimental validation."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1 • FLT3 • MIR150 • MIR335 • RUNX1

Dapolsertib: (Ryvu Therapeutics Press Release) - "In March 2025, the first patient was dosed with dapolsertib (MEN1703, SEL24) in the Phase II JASPIS-01 study, treating patients with relapsed/refractory Diffuse Large B-cell Lymphoma (r/r DLBCL) as a monotherapy and in combination with glofitamab. JASPIS-01 is fully funded by the Menarini Group and operationally executed by Ryvu."

Trial status • Non-Hodgkin’s Lymphoma

DBY-Tobacco: a dual-branch model for non-tobacco related materials detection based on hyperspectral feature fusion. (PubMed, Front Plant Sci) - "We created a dataset of 1,000 images containing 4,203 NTRMs by using a hyperspectral camera, SpectraEye (SEL-24), with a spectral range of 400-900 nm...Future work will focus on addressing limitations such as stripe noise in HSI and expanding the detection to other types of NTRMs. The dataset and code are available at: https://github.com/Ikaros-sc/DBY-Tobacco."

Journal • IKZF1

MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01) (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Ryvu Therapeutics SA | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Dual PIM/FLT3 Inhibitor MEN1703 Combines Synergistically With Gilteritinib in FLT3-ITD-Mutant Acute Myeloid Leukaemia. (PubMed, J Cell Mol Med) - "We also show that MEN1703 downregulates stromal cytokines that promote cytokine-mediated resistance of AML blast cells to FLT3 inhibition. These results demonstrate the importance of the combination approach to overcome microenvironment-mediated resistance to FLT3 inhibitors."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Ryvu Therapeutics has commissioned a €3.82 million Phase II clinical trial of MEN1703 (SEL24) [Google translation] (Investing.com) - "Ryvu Therapeutics has commissioned Syneos Health LLC from the United States and Syneos Health UK Limited from England to conduct the JASPIS-01 clinical trial. This is a Phase II clinical trial that will evaluate the safety and efficacy of MEN1703 (SEL24) as a single agent and in combination with glofitamab in the treatment of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The value of the contract is EUR 3.82 million, the company reported...The JASPIS-01 study is scheduled to begin in Q4 2024, and start-up activities are already underway. The study will begin initially at clinical sites in Poland, with plans to expand to additional EU and non-EU countries still as part of Part 1."

Commercial • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01) (clinicaltrials.gov) - P2 | N=178 | Not yet recruiting | Sponsor: Ryvu Therapeutics SA

Combination therapy • Monotherapy • New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Ryvu Therapeutics Presents Preclinical Data on RVU120 and Synthetic Lethality Programs at the 2024 AACR Annual Meeting (PRNewswire) - "Ryvu Therapeutics...presents preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24) at the 2024 AACR Annual Meeting, April 5-10 in San Diego, California....RVU120, a highly selective and potent CDK8/19 inhibitor, shows potential efficacy as both monotherapy and in combination with ruxolitinib (RUX), a JAK1/2 inhibitor, for the treatment of myeloproliferative neoplasms (MPN) and polycythemia vera (PV).... MEN1703 (SEL24) demonstrates efficacy both as a monotherapy and in combination with the JAK inhibitor ruxolitinib (RUX) in preclinical models of myelofibrosis (MF). MEN1703 demonstrated anti-tumoral efficacy in MF preclinical models, exhibiting in vitro activity at clinically relevant concentrations. Notably, the combination of MEN1703 with the standard of care, RUX, exhibited synergistic effects and molecular analyses confirmed the inhibition of downstream targets of PIM."

Preclinical • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

MEN1703/SEL24 exhibits promising antitumoral activity in preclinical models of myelofibrosis both as single agent and combined with ruxolitinib (AACR 2024) - "MEN1703/SEL24 (MEN) is an oral, first-in-class, dual PIM/FLT3 kinase inhibitor in development for hematologic malignancies.This study aims to investigate the efficacy of MEN alone and in combination with the JAKi ruxolitinib (RUX) in preclinical MF models and to elucidate the underlying signaling pathways.MF cell lines (JAK2V617F and JAK2 wild type) were used in MTS assays to assess the in vitro cytotoxicity of MEN alone and in combination with RUX, compared with the PIM inhibitor TP-3654 (Dutta 2022). Importantly, MEN combined with the standard of care RUX was synergistic, and molecular analyses confirmed the role of PIM downstream target inhibition. Our results support the therapeutic potential and relevance of MEN in MF treatment strategies."

Preclinical • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • FLT3 • MCL1 • PIM1

Ryvu Therapeutics Summarizes 2023 Fiscal Year and Provides Corporate Update (PRNewswire) - "A Phase II study in DLBCL is scheduled to begin in mid-2024. The goal is to evaluate the activity of MEN1703 (SEL24) as monotherapy and in combination with standard therapy in patients with DLBCL....The study will be initiated based on the potent activity of MEN1703 (SEL24) observed in preclinical lymphoma models. Clinical trials have confirmed the acceptable safety profile and early signs of activity of MEN1703 (SEL24) as a monotherapy. Based on the available data, further program development will continue in patients with DLBCL and potentially in additional indications....Ryvu will attend the AACR Annual Meeting (San Diego, USA) from April 5-10, 2024, to present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24)."

New P2 trial • Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma

Ryvu Therapeutics to Present Preclinical Data on RVU120 and Synthetic Lethality Programs at the 2024 AACR Annual Meeting (PRNewswire) - "Ryvu Therapeutics...announced today that preclinical data from its synthetic lethality pipeline and RVU120 project, as well as on MEN1703 (SEL24), will be presented at the upcoming 2024 AACR Annual Meeting, scheduled for April 5-10 in San Diego, California...Updated preclinical data will be presented from Ryvu’s synthetic lethality pipeline, including PRMT5 inhibitors in MTAP-Deficient cancers, WRN inhibitors for the treatment of microsatellite unstable (MSI-H) tumors, and Ryvu’s cutting-edge synthetic lethality platform based on primary cancer cells; Poster presentation to highlight the synergistic effects of RVU120 in combination with ruxolitinib in myeloproliferative neoplasms; Ryvu’s partner Menarini to present data on MEN1703 (SEL24), demonstrating promising anti-tumor activity in preclinical models of myelofibrosis both as a single agent and combined with ruxolitinib."

Preclinical • Synthetic lethality • Colorectal Cancer • Microsatellite Instability • Myelofibrosis • Myeloproliferative Neoplasm • Solid Tumor

Ryvu Therapeutics Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Expanded development of MEN1703 (SEL24) with global licensee, Menarini, for a new study in advanced diffuse large B-cell lymphoma (DLBCL): Initiation of the Phase II study in DLBCL is expected in H1 2024."

New P2 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Ryvu Therapeutics Presents Preclinical Data on PRMT5 and its Synthetic Lethality Platform at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Ryvu Therapeutics...announced presentations of preclinical data from the PRMT5 program and synthetic lethality platform, as well as preclinical data on MEN1703 (SEL24) in B-cell lymphomas, at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place in Boston, Massachusetts....The novel, optimized inhibitors exhibit a significantly improved PK profile, and in addition, the compounds show antitumor efficacy and target engagement in vivo, providing a strong foundation for further development....Pharmacological inhibition with MEN1703 (SEL24), a first-in-class, oral, dual type I PIM/FLT3 inhibitor shows anti-proliferative effects in B cell lymphomas of various histotypes."

Preclinical • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Ryvu Therapeutics to Present Preclinical Data on PRMT5 and its Synthetic Lethality Platform at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Ryvu Therapeutics...announced that preclinical data from its PRMT5 program and synthetic lethality platform as well as preclinical data on MEN1703 (SEL24) in B-cell lymphomas will be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 11-15 in Boston, Massachusetts....Poster presentations highlight preclinical data from Ryvu’s PRMT5 program in MTAP-Deficient cancers and its synthetic lethality platform in colorectal cancer models....Preclinical efficacy data of MEN1703 (SEL24) in B-cell lymphomas to be presented by Ryvu’s partner Menarini."

Preclinical • Colorectal Cancer • Non-Hodgkin’s Lymphoma

MEN1703/ SEL24, a potent PIM inhibitor, demonstrates promising anti-tumour activity in activated B cell like diffuse large B cell lymphoma, mantle cell lymphoma and marginal zone lymphoma cells. (AACR-NCI-EORTC 2023) - No abstract available

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Ryvu Therapeutics' Global Licensee Menarini to Expand Development of MEN1703 (SEL24) with a New Study in Advanced Diffuse Large B-Cell Lymphoma (DLBCL) (PRNewswire) - "Ryvu Therapeutics...announced that Ryvu's licensee, the Menarini Group, will expand development of MEN1703 (SEL24) by initiating a new Phase II study in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in addition to continued translational work in other hematologic indications....The Phase II study, which will explore the activity of MEN1703 in combination with standard-of-care therapy in DLBCL and as a single agent, is being initiated based on strong preclinical activity of MEN1703 in lymphoma....Phase II Study to be Initiated in H1 2024."

New P2 trial • Diffuse Large B Cell Lymphoma

DIAMOND-01: SEL24/MEN1703 in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=73 | Completed | Sponsor: Menarini Group | Active, not recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ May 2023 | Trial primary completion date: Sep 2022 ➔ May 2023

Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Ryvu Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Upcoming clinical and corporate milestones... (i) SEL24 (MEN1703): Updates from the Phase I/II study of SEL24/MEN1703, a first-in-class dual PIM/FLT3 kinase inhibitor, in patients with IDH1/2-mutated acute myeloid leukemia expected in 2023; (ii) Synthetic lethality: Updated in vivo data for the MTA-cooperative PRMT5 inhibitors will be presented at the upcoming 2023 AACR Annual Meeting in Orlando, Florida."

P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

PIM Inhibition By SEL24/MEN1703 Combines Synergistically with Gilteritinib in FLT3-ITD Preclinical Models of Acute Myeloid Leukemia (ASH 2022) - P1/2 | "The higher efficacy of this combination in-vivo and compared to monotherapy could be related to a very potent concomitant inhibition of FLT3 and PIM kinases affecting upregulated FLT3 signaling pathway in-vivo as demonstrated by the reduction of phosphorylation of downstream effector proteins, such as pS6. Overall, these experiments have demonstrated the antitumor potential of concomitant inhibition of FLT3 and PIM kinases which could drive a novel therapeutic strategy in AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • FLT3 • MYC

MEN1703-Mediated PIM Kinases Inhibition Impairs Protumoral and Immunosuppressive Phenotype and Functions of Macrophages in Classical Hodgkin Lymphoma (ASH 2022) - "Our data suggest that PIMs support pro-tumoral and immunosuppressive phenotype of cHL-TAMs. Since PIM activity is required for RS cell survival and immune escape, these kinases are rational targets for therapy in cHL, suggesting the use of PIM inhibitors, such as MEN1703, as a possible therapeutic approach ."

IO biomarker • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Immunology • Inflammation • Lymphoma • Oncology • CD163 • CHI3L1 • CREB1 • CSF1 • CSF1R • FLT3 • GLI2 • MMP1 • MRC1 • PDGFB • PIM1 • STAT3 • TGM2

Super-Enhancer-Driven PIM Kinase Upregulation in Multiple Myeloma Maintains the Plasma Cell-Specific Oncogenic and Microenvironmental Circuits, and Can be Efficiently Targeted By the Pan-PIM Inhibitor MEN1703 (ASH 2022) - "BET inhibitor JQ1, which disrupts super-enhancer assembly, downregulated PIM kinase expression. The clinical utility of next generation/more potent PIM inhibitor in MM should be re-investigated. Study supported by National Science Centre Grants PRELUDIUM 2018/31/N/NZ5/03214, ETIUDA 2020/36/T/NZ5/00610 and Ministry of Science and Higher Education Diamond Grant DI2015 007145."

Hematological Malignancies • Multiple Myeloma • Oncology • FLT3 • IRF4 • MYC • PIM1 • PIM3 • RHOA

PIM Kinases Regulate Super-Enhancer-Dependent Gene Expression in Diffuse Large B-Cell Lymphoma (ASH 2022) - "They also indicate that PIM inhibition with MEN1703 can be a therapeutic option in DLBCL. Study supported aby Foundation For Polish Science TEAM Grant # POIR.04.04.00-00-5C84/17 and Polish National Science Centre Grant # 2018/29/B/NZ5/01471."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BRD4 • FLT3 • KAT8 • PIM1 • PIM3

Ryvu Therapeutics Presents Clinical and Translational Data of RVU120 and SEL24 (MEN1703) at the 2022 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Combination therapy of SEL24 (MEN1703) with gilteritinib, a highly potent and selective oral FLT3 inhibitor, induces strong tumor regression and complete responses in vivo, demonstrating the potential of concomitant FLT3 and PIM inhibition kinases in AML. SEL24 (MEN1703)-induced PIM inhibition, and the mechanism of action was also demonstrated in vitro in multiple myeloma (MM), classical Hodgkin lymphoma-tumor-associated macrophages (cHL-TAMs), and diffuse large B-cell lymphoma (DLBCL) models. In multiple myeloma preclinical models, SEL24 (MEN1703) induces cytotoxicity of MM cell lines, disrupts MM endothelial cell vessel formation, and decreases the activity of several pathways essential for myeloma cell survival. This study demonstrates the promising therapeutic potential of SEL24 (MEN1703) in MM and reveals the underlying mechanism of PIM inhibition. Indeed PIM-dependent oncogenic signaling pathways were also inhibited following SEL24 (MEN1703) treatment of MM cells."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1/2 Study of SEL24/MEN1703, a First-in-Class Dual PIM/FLT3 Kinase Inhibitor, in Patients With IDH1/2- Mutated Acute Myeloid Leukemia: The DIAMOND-01 Trial (SOHO 2022) - P1/2 | "SEL24/MEN1703 had a manageable safety profi le and single-agent activity in adult patients with R/R IDHm AML and may be a feasible therapeutic option in this diffi cult-to-treat population."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH1 • IDH2