Qinprezo (vosaroxin) / Royalty, Viracta Therap, Denovo, Xoma - LARVOL DELTA

Impact of midostaurin in younger AML patients intensively treated with high-dose anthracycline (ASH 2025) - P2/3 | "Introduction:Midostaurin (MIDO) was approved by the FDA in 04/2017 for the treatment of FLT3 mutated AMLpatients in combination with intensive chemotherapy (ICT) with daunorubicin (DAUNO) administered at60 mg/m² for 3 days based on the findings of the RATIFY trial (Stone, NEJM 2017)...The aim of this post-hoc studywas to assess the impact of MIDO in combination with higher-dose anthracyclines (DAUNO or idarubicin)in the BIG-1 trial (Hunault, NEJM Ev 2025).Between 01/2015 and 07/2021, the BIG-1 trial (NCT02416388) included patients (pts) aged 18-60 yearswith newly diagnosed AML treated with ICT (CBF-AML and APL excluded)...Of note, MIDO was omitted during the post-induction cycles in the few pts whoentered nested randomized studies evaluating dexamethasone (N=46) or vosaroxin (N=13) incombination with HDAC or IDAC, respectively.Overall, 382 (84.7%) pts had FLT3-ITD, 83 (18.4%) had a TKD mutation and 14 had both, leading to theinclusion of 451 pts in this..."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • FLT3 • NPM1

A Novel Anticancer Quinolone, ( R)-Wac-224 Monotherapy or Combination with Cytarabine/Venetoclax Confers Promising Activities Against Acute Myeloid Leukemia (ASH 2023) - "Quinolones, antibacterials that attack DNA gyrase and topoisomerase IV (functional analog of mammalian Top2), possess a broad spectrum chemotherapeutic activities including anti-leukemic effects (e. g. vosaroxin)...Whereas, WAC did neither increase serum troponin-T nor decrease the crypt numbers in the small intestine, indicating WAC was less toxic than doxorubicin...R-WAC and cytarabine or daunorubicin and cytarabine did not exhibited decreased body weight in mice...ConclusionR-WAC has promising anti-leukemia effects with less toxicities compared with conventional anthracycline possibly due to the different inhibitory mechanisms of Top2 isoform (anthracycline inhibits Top2β). These results indicate that R-WAC is a promising therapeutic agent for AML and support its clinical development, especially as a combination of R-WAC with cytarabine or venetoclax."

IO biomarker • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • TOP2A

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=42 | Completed | Sponsor: Vanderbilt-Ingram Cancer Center | Active, not recruiting ➔ Completed

Trial completion • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

Discovery of Voreloxin as a Dual-Selective Stabilizer for c-Myc/Bcl-2 G-Quadruplexes in Leukemia. (PubMed, Chem Biol Drug Des) - "Molecular docking, molecular dynamics (MD) simulations, and MM/GBSA calculations further confirmed the stable binding of voreloxin to both c-Myc and Bcl-2 G4s, primarily driven by π-π stacking and hydrogen bonding interactions. These findings provide valuable insights for the development of G4-targeting drugs for cancer therapy."

IO biomarker • Journal • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • BCL2 • MYC

Evaluation of the Antibacterial and Antioxidant Properties of Chemical Constituents of the Roots of Woodfordia uniflora: An Integrated Approach of Experimental and Computational Study. (PubMed, Biochem Res Int) - "The antibacterial activity result indicated that the oil extract had promising activity against P. aeruginosa, E. coli, S. pyogenes, and S. aureus with IZ of 14.3 ± 0.81, 15.0 ± 0.0, 15.6 ± 0.47, and 17.6 ± 0.47 mm, respectively, at 5 mg/mL, compared to ciprofloxacin (1Z 27-30.0 ± 0.0 mm) at 30 μg/mL...Toward the PDB ID: 4FM9 receptor, β-sitosterol (2) and compound 3 exhibited the best binding free energy of -9.1 and -9.8 kcal·mol, respectively, compared to vosaroxin (-7.8 kcal/mol)...The in silico toxicity analysis showed none of the compounds would be cytotoxic, mutagenic, or hepatotoxic. The in vitro antioxidant and antibacterial results supported by in silico analysis demonstrated that the roots of W. uniflora have the potential to be therapeutic agents for bacterial infections and free radical-inducing diseases."

Journal • Hepatology • Infectious Disease • Malaria

BIG-1: Study to Improve OS in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus MMF Prophylaxis of GvHD in Allografted Patients in First CR (clinicaltrials.gov) - P2/3 | N=3100 | Recruiting | Sponsor: University Hospital, Angers

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • NPM1

(R)-WAC-224, A NOVEL ANTICANCER QUINOLONE AND VENETOCLAX PLUS AZACITIDINE OVERCOME VENETOCLAX-RESISTANT AML VIA DOWNREGULATION OF MCL-1 (EHA 2024) - "* Hypomethylating agents (azacytidine,AZA or decitabine) and venetoclax (VEN), a selective BCL-2 inhibitor, became one of the standard treatmentsfor transplant- ineligible patients with AML, yielding high response rates and durable remission, with a goodsafety profile; therefore, treatment failure due to VEN resistance may be critical... WAC inhibited TOP2α comparable with vosaroxin (a known Top2 inhibitor) in a topoisomerase relaxationassay...WACdid neither increase serum troponin-T (doxorubicin: 60... R-WAC has promising anti-leukemia effects with less toxicities compared with conventional anthracycline. R-WAC possibly overcomes VEN resistance via MCL-1 downregulation."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Mantle Cell Lymphoma • Oncology • MCL1 • TOP2A

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Vanderbilt-Ingram Cancer Center | Trial completion date: Apr 2024 ➔ Sep 2024

Combination therapy • Trial completion date • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Vanderbilt-Ingram Cancer Center | Trial completion date: Jan 2024 ➔ Apr 2024

Combination therapy • Trial completion date • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2023 ➔ Jan 2024

Combination therapy • Trial completion date • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

VOSAROXIN PLUS AZACITIDINE TREATMENT FOR PATIENTS WITH MYELODYSPLASTIC SYNDROME (MDS): A PHASE 1/COHORT EXPANSION STUDY (EHA 2017) - "The MTD of vosaroxin in MDS patients was 34 mg/m2/d when given on Days 1 and 4 with a fixed dose of 75 mg/m2 of azacitidine on Days 1-7. The major non-hematologic toxicities were infections, febrile neutropenia, and bleeding. The combination of vosaroxin and azacitidine showed promising activity with responses rates comparable or better than those generally observed with azacitidine alone."

Clinical • Biosimilar • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Oncology

Prediction of Early Mortality with Non-Intensive Acute Myeloid Leukemia (AML) Therapies: Analysis of 1336 Patients from MRC/NCRI and SWOG (ASH 2021) - "Treatments included: Low dose Ara-C (LDAC) alone, sapacitabine alone and LDAC in combination with vosaroxin, tosedostat or ganetespib (MRC/NCRI); Azacytidine (AZA) alone, tipifarnib alone, and AZA in combination with mylotarg, midostaurin, and nivolumab (SWOG). Our ability to predict early death in older patients treated with lower intensity AML therapies is limited with routinely available clinical variables. Inclusion of cytogenetic risk, FLT3-ITD, and NPM1 mutation status minimally improved the prognostic accuracy as did some of the QLQ-C30 subscales. Our data highlight the difficulties in predicting outcomes with non-intensive AML therapy with routinely available baseline clinical information."

Clinical • Acute Myelogenous Leukemia • Anorexia • Fatigue • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • NPM1

[VIRTUAL] Comparison of a Combination of Vosaroxin (VOS) and Intermediate-Dose Cytarabine (IDAC) with Idac for the Consolidation Therapy of Younger Patients with Favorable- and Intermediate-Risk Acute Myeloid Leukemia (AML) in First Complete Remission (CR): Preliminary Results of a Randomized Phase 2 R4-VOS Study of the French ALFA-Filo AML Intergroup (ASH 2020) - "The trial design includes several randomizations (R): Idarubicin vs daunorubicin for induction (R1), HDAC vs IDAC for consolidation (R2), post-transplant GVHD prophylaxis modalities (R3). The phase 3 part of the trial will not open. The BIG-1 trial is still ongoing and uses the same design to tests addition of other drugs to the IDAC/HDAC consolidation backbone."

Clinical • P2 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Transplantation • FLT3 • NPM1

The VITAL Trial: Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of acute Myeloid Leukemia (ASH 2019) - P2; "The combination of Vos and iAC in newly diagnosed AML pts appears safe. Mucocutaneous complications were observed as noted in previous studies with Vos. Administration of oral cryotherapy during Vos administration appeared to reduce occurrence of oral mucositis during induction, but > Gr 3 neutropenic enterocolitis occurred in 7/42 (17%) pts."

P2 data • TP53

Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of Acute Myeloid Leukemia (VITAL) Patients Eligible for Intensive Chemotherapy: A Planned Interim Analysis (ASH 2017) - P2; "Aside from the recent approval of midostaurin for FLT3-mutated AML, the induction strategy for the majority of intensive-chemotherapy eligible pts has remained unchanged for nearly 4 decades. The combination of vosaroxin and infusional cytarabine in newly diagnosed AML pts appears safe with mucocutaneous complications observed that have been previously noted in studies of vosaroxin. The administration of oral cryotherapy during vosaroxin administration appeared to reduce occurrence of mucositis during induction. Neutropenic enterocolitis did occur at a rate consistent with standard induction chemotherapy but continues to be monitored closely."

Adverse events • Clinical • P2 data • Acute Myelogenous Leukemia • Biosimilar • Immunology

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2022 ➔ Jul 2023

Combination therapy • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

In vitro Antiproliferative Properties of Lipophililic -Acid Chelating Fluoroquinolones and triazoloFluoroquinolones with 7-dihaloanilinosubstitution. (PubMed, Anticancer Agents Med Chem) - "Objectives As antineoplastic Vosaroxin is a commercial fluoroquinolone (FQ); we hypothesize that superlative antiproliferation activity of lipophilic FQs/TFQs series correlate to their acidic groups and C8-C7 ethylene diamine Chelation Bridge along with bulky dual halogenations...Parameters including potency, toxicity, and selectivity (potency/toxicity) have been reported along with DPPH- and NO- radicals' scavenging propensities -as their molecular action mechanism- in comparison to ascorbic acid and indomethacin respectively...Explicitly 4a, 3a and 4c exerted exquisite antiinflammation-selective cytotoxicity duality in vitro. Conclusions Such new potential chelation mechanism can explain the pronounced difference in antineoplastic activity of new FQs/TFQs."

Journal • Preclinical • Cervical Cancer • Hematological Malignancies • Immunology • Inflammation • Leukemia • Lung Cancer • Oncology • Pancreatic Cancer

Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2021 ➔ Apr 2024

Trial completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2; N=42; Active, not recruiting; Sponsor: Vanderbilt-Ingram Cancer Center; Trial completion date: Jul 2021 ➔ Jul 2022

Clinical • Combination therapy • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC

Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants. (PubMed, Adv Appl Bioinform Chem) - "Dichloromethane roots extract of U. scheffleri showed potent antibacterial activity against S. aureus (MIC = 6.25 µg/mL) compared to gentamicin (MIC=5 µg/mL). In silico, molecular docking analysis of compounds (1and 3-5) showed strong interaction with E. coli DNA gyrase B with a binding energy value ranging from -6.9 to -6.0 kcal/mol compared to ciprofloxacin -7.2 kcal/mol, whereas analysis against human topoisomerase IIα showed binding energy value ranging from -5.9 to -5.3 kcal/mol compared to vosaroxin (-6.2 kcal/mol)...The ADMET studies showed the highest drug-likeness properties for studied compounds other than bis(2-ethylheptyl) phthalate (3). DFT calculations suggested that studied compounds showed the lowest gap energy and were chemically reactive, and isolated compounds may serve as potential drug candidates that corroborate with the traditional uses of studied plants."

Journal • Asthma • Dermatology • Immunology • Infectious Disease • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Novel Class of Functionalized Synthetic Fluoroquinolones with Dual Antiproliferative - Antimicrobial Capacities. (PubMed, Asian Pac J Cancer Prev) - "As vosaroxin as a fluoroquinolone (FQ) had anticancer effectiveness; this study aimed to screen new lipophilic FQs for their dual antimicrobial-antiproliferative activities. Using sulforhodamine B assay; 36 lipophilic FQs have been screened for antimicrobial propensities against S. aureus, E. coli, and C. albicans vs. the respective references ciprofloxacin and fluconazole...Normal periodontal ligament fibroblasts (PDL) were tested for safety examination in comparison to the cisplatin...The reduced 4e and 4f compounds have shown nanomolar inhibition against K562 (as of 4e), PANC-1 and MCF-7 (as of 4f) with IC50 values of 0.005, 0.11 and 0.30 µM, respectively. Succinctly FQs' dual gram-positive antibacterial-antineoplastic capacities expand on of drug design scaffolds in lead generation.."

Journal • Breast Cancer • Hematological Malignancies • Infectious Disease • Leukemia • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2; N=68; Completed; Sponsor: M.D. Anderson Cancer Center; Active, not recruiting ➔ Completed

Clinical • Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study of Vosaroxin With Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2 (clinicaltrials.gov) - P2; N=9; Completed; Sponsor: University of Ulm; Recruiting ➔ Completed; N=168 ➔ 9; Trial completion date: Dec 2021 ➔ Oct 2019; Trial primary completion date: Dec 2021 ➔ Oct 2019

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

VITAL: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2; N=42; Active, not recruiting; Sponsor: Vanderbilt-Ingram Cancer Center; Trial completion date: Jul 2020 ➔ Jul 2021

Clinical • Combination therapy • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • SRC