E2082 / Eisai - LARVOL DELTA

A Novel Inhibitor of FLT3 and Its Drug-Resistant Mutants with Superior Activity to Gilteritinib in Molm-13 Preclinical Acute Myeloid Leukemia Xenograft Model (ASH 2022) - "Several FLT3 inhibitors have been developed such as the first generation multikinase inhibitor Midostaurin which is approved for newly diagnosed FLT3 mutant AML in combination with induction chemotherapy...Herein we describe 2082-0047, a novel tyrosine kinase inhibitor with sub-nanomolar potency against FLT3 mutant AML, including TKD mutations...Our non-GLP in vivo safety studies confirmed a broad therapeutic window of 2082-0047. Ongoing Investigational New Drug (IND) enabling studies will include comparing the effect of 2082-0047 to gilteritinib in an immunocompetent syngeneic AML murine model harboring both a Flt3-ITD and F691 TKD gatekeeper mutation."

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

"@Tyme20820796 @CauleyTyme @learningnewinfo @Byrd_Life4L @LADYDAYDAO" (@TYMEinc_)

EFFECTS OF PRIOR ANTIBIOTIC USE ON NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN PATIENTS ADMITTED WITH PNEUMONIA TO PATAN HOSPITAL, NEPAL (ISPPD 2022) - "Results Of the 2082 children with pneumonia, 613 (29.4%) did not receive any antibiotics prior to swabbing, 510 (24.5%) and 532 (25.6%) received prior antibiotics at home or in hospital, respectively...Conclusions Our results show an inverse relationship between antibiotic use and pneumococcal carriage. Access to antibiotics may lead to underestimation of nasopharyngeal pneumococcal carriage rates."

Clinical • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Author Correction: Correlation between expression levels of lncRNA UCA1 and miR-18a with prognosis of hepatocellular cancer. (PubMed, Eur Rev Med Pharmacol Sci) - "The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20820."

Biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • MIR18A • UCA1

Pneumocystis Jirovecii Infection in Autologous Hematopoietic Stem Cell Transplant Recipients (TCT-ASTCT-CIBMTR 2022) - "Results Of the 2082 patients undergoing autologous HSCT, 704 patients (33.8%) received PJP prophylaxis in the first 6 months following transplant...Trimethoprim-sulfamethoxazole (TMP-SMX) was the most used prophylaxis agent (70.3%), followed by inhaled pentamidine (31.8%), with intravenous pentamidine (8.1%), dapsone (7.1%), and atovaquone (2.6%) being used less frequently...This was the case even with relatively modest rates of PJP prophylaxis in the first 6 months following transplant. Most cases of PJP occurred in patients receiving additional immunosuppression and rarely occurred in the first 3 months after transplant."

Clinical • Bone Marrow Transplantation • Infectious Disease • Pneumonia • Respiratory Diseases • Transplantation

"TGIF @SU2C @PCFnews @TeenCancerUSA @AmericanCancer @lex_DAO @joinupstream @OURrescue @treehumper22 @Tyme20820796 @btfmediaco @adorbs_disrupts @sniper_projects @MG77588984 @tylerperry @The_BluntHeads @FINALLEVEL @DefiantPixel @Mikeyyy_G20 @TheMetaFactory @syndicate_dao @JackALaing" (@CauleyTyme)

Oncology

Prism (II): 127 cooling dummy experiments. (PubMed, Forensic Sci Int) - "A total of 127 dummy cooling experiments were conducted (total cooling time 2082 h, average cooling time 24.6 h) for both regular and elevated starting temperatures, covering ambient temperatures between - 14.0 °C and + 24.0 °C and for different cooling conditions...In the future it may potentially be adapted to known conditions. Our results indicate that Prism's cooling weight might serve as a highly individual, case-based data-driven umbrella parameter, replacing (subjectively) estimated parameters."

Journal

Pneumocystis Jirovecii Infection in Autologous Hematopoietic Stem Cell Transplant Recipients (ASH 2021) - "Results Of the 2082 patients undergoing autologous HCT, 704 patients (33.8%) received PJP prophylaxis in the first 6 months following transplant...Trimethoprim-sulfamethoxazole (TMP-SMX) was the most used prophylaxis agent (70.3%), followed by inhaled pentamidine (31.8%), with intravenous pentamidine (8.1%), dapsone (7.1%), and atovaquone (2.6%) being used less frequently...In 8 of 9 cases, patients were receiving concurrent pharmacologic immunosuppression in the form of steroids or maintenance brentuximab (Table 1)...This was the case even with relatively modest rates of PJP prophylaxis in the first 6 months following transplant. Most cases of PJP occurred in patients receiving additional immunosuppression and often occurred late following transplant."

Clinical • Bone Marrow Transplantation • Critical care • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Transplantation • PCR

[VIRTUAL] Haemophilia A Genotyping in Patients with Discrepancy in FVIII Activity Levels Measured with One-stage and Chromogenic Assays (ISTH 2021) - "Two of them were not reported (c.6246C>A/p.(Ser2082Arg); c.5508G>T/p.(Trp1836Cys)), whereas the reported ones were associated with different (mild-moderate-severe) phenotypes but only based on presumed OSA (Table 1). Conclusions : Thus far, in EAHAD database, only 28 missense HA-causative variants were associated with FVIII:C assay discrepancy, and none of them matched with our 5 cases from Argentina, which showed different phenotype severities in EAHAD when were reported. Our data may reveal some degree of misclassification of phenotype severity in HA, which may be associated with the rare application of CSA to measure FVIII:C complementing OSA levels.Consequently, our findings reinforce the convenience to base the initial diagnosis of non-severe-HA phenotype on the results of both, one-stage and chromogenic assays."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2082 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=118; Terminated; Sponsor: Eisai Co., Ltd.; Suspended ➔ Terminated; Safety Review

Clinical • Trial termination

Genetic Mapping and Validation of Loci for Kernel-Related Traits in Wheat (Triticum aestivum L.). (PubMed, Front Plant Sci) - "Phenotypic data from six environments and a Wheat55K single-nucleotide polymorphism array-based constructed genetic linkage map from a recombinant inbred line population derived from the cross between the wheat line 20828 and the line SY95-71 were used to identify quantitative trait locus (QTL) for kernel length (KL), kernel width (KW), kernel thickness (KT), thousand-kernel weight (TKW), kernel length-width ratio (LWR), KS, and factor form density (FFD)...A few predicted genes involved in regulation of kernel growth and development were identified in the intervals of these identified major QTL. Taken together, these stable and major QTLs provide valuable information for understanding the genetic composition of kernel yield and provide the basis for molecular marker-assisted breeding."

Journal • PCR

Role of fasting duration and weekday in incretin and glucose regulation. (PubMed, Endocr Connect) - "This cross-sectional study is based on data from the ADDITION-PRO study, where 2082 individuals attended a health examination including an OGTT...In this study longer overnight fasting duration was associated with a worsening of glucose tolerance and increased incretin response to oral glucose. We found higher fasting insulin levels on Mondays compared to the other days of the week, potentially indicating worsened glucose regulation after the weekend."

Journal

A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy (clinicaltrials.gov) - P2; N=8; Terminated; Sponsor: Eisai Inc.; Completed ➔ Terminated; Safety Review

Clinical • Trial termination • CNS Disorders • Epilepsy

Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis. (PubMed, Clin J Am Soc Nephrol) - "Fruit and vegetable intake in the hemodialysis population is low and a higher consumption is associated with lower all-cause and noncardiovascular death."

Clinical • Journal • Allergy • Asthma • Cardiovascular • Chronic Kidney Disease • Immunology • Nephrology • Respiratory Diseases

Newly added product (Eisai Press Release) - P1, Epilepsy

Pipeline update • CNS Disorders • Epilepsy

Bioinformatics Analysis for Multiple Gene Expression Profiles in Sepsis. (PubMed, Med Sci Monit) - "RESULTS There were 2082 DEGs between blood samples of sepsis patients and controls, 2079 DEGs between blood samples of septic shock patients and healthy individuals, 6590 DEGs between neutrophils from sepsis and controls, and 1056 DEGs between neutrophils from septic shock patients and normal controls...RNF4 was a hub gene from PPI analyses based on datasets from neutrophils and RNF4 (AUC=0.909) was capable of distinguishing neutrophil samples from septic shock samples and controls. CONCLUSIONS Our findings identified several key genes and pathways related to sepsis development."

Biomarker • Journal

Latent Tuberculosis Infection among Healthcare Students and Postgraduates in a Mediterranean Italian Area: What Correlation with Work Exposure? (PubMed, Int J Environ Res Public Health) - "Latent TB is relatively low among medical school students in our geographic area. Nevertheless, this infectious disease must be regarded as a re-emerging biohazard for which preventive strategies are required to limit the risk of infection, especially among exposed workers."

Journal

Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2082 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=118; Suspended; Sponsor: Eisai Co., Ltd.; Trial completion date: Aug 2019 ➔ Mar 2020; Trial primary completion date: Aug 2019 ➔ Mar 2020

Clinical • Trial completion date • Trial primary completion date

Tet methylcytosine dioxygenase 1 promotes hypoxic gene induction and cell migration in colon cancer. (PubMed, J Cell Physiol) - "We also identified two novel gene mutants of TET1 in 120 paired tumor/normal tissue specimens by DNA sequencing and found that TET1 E2082K mutant blocked the TET1-enhanced cell migration. Our results showed that the downregulation of TET1 rescued the abnormally high levels of gene expression resulting from hypoxia in tumors and reduced the migration activity of tumor cells, suggesting a therapeutic role by interference with TET1 in colon cancer treatment. By demonstrating that hypoxia upregulated TET1 and that TET1 drove HIF-1α-responsive genes, we showed that an epigenetic mechanism and tumor microenvironment-driven models coexisted and mutually affected colon cancer."

Journal

A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy (clinicaltrials.gov) - P2; N=9; Completed; Sponsor: Eisai Inc.; Suspended ➔ Completed; Trial completion date: Nov 2019 ➔ Jun 2019; Trial primary completion date: Nov 2019 ➔ Jun 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

ACUTE HEPATITIS E VIRUS INFECTION - EXPECT WHEN YOU ARE NOT EXPECTING (UEGW 2019) - "Elevated transaminases and bilirubin were detected: aspartate transaminase 994 U/l, alanine transaminase 2082 U/l, alkaline phosphatase 387 U/l, gamma glutamyltransferase 466 U/l, total bilirubin 162 µmol/l)... HEV should be considered as an etiologie agent in patients with acute hepatitis when HAV, HBV, HCV, CMV, EBV virus infections, medication-induced and autoimmune injuries are excluded. Strict hygienic recommendations (hand hygiene), avoiding consumption of undercooked meat (pork, wild boar and venison), and polluted water are the basic measures of prevention [1]."

Identification and validation of a novel major QTL for all-stage stripe rust resistance on 1BL in the winter wheat line 20828. (PubMed, Theor Appl Genet) - "Three minor stable QTL (located on chromosomes 1B, 4A and 6A, respectively) also added to the resistance level of QYr.sicau-1B.1. Our results provide valuable information for further fine mapping and cloning as well as molecular-assisted breeding with QYr.sicau-1B.1."

Journal

A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy (clinicaltrials.gov) - P2; N=9; Suspended; Sponsor: Eisai Inc.; Trial completion date: Aug 2019 ➔ Nov 2019; Recruiting ➔ Suspended; Trial primary completion date: Aug 2019 ➔ Nov 2019

Trial completion date • Trial primary completion date • Trial suspension

Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2082 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=118; Suspended; Sponsor: Eisai Co., Ltd.; Recruiting ➔ Suspended

Trial suspension

Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2082 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=118; Recruiting; Sponsor: Eisai Co., Ltd.; Trial completion date: Feb 2019 ➔ Jul 2019; Trial primary completion date: Feb 2019 ➔ Jul 2019

Clinical • Trial completion date • Trial primary completion date