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YM BioSciences, Inc. Ordinary S Message Board

  • errataqwerty errataqwerty Dec 7, 2012 3:44 PM Flag

    YMI - 2 CYT387 presentations on Sunday

    Phase I/II Study of CYT387, a JAK1/JAK2 Inhibitor for the Treatment of Myelofibrosis

    Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response

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    • Do we get a press release today at start of presentation?

    • incy will present more data on their jakafi drug....this could get real interesting. "performance is difficult to rate, unless one has something to compare it to" . may take a little time to quantify all the data from 12/2011 to 12/2012 concerning cyt387 vs old to new incy data.JMHO

      Sentiment: Hold

    • Will try posting this one more time.
      The 2nd program is scheduled for 5:30 today
      from the summary:

      The current preliminary analysis suggests that genes relevant to immune response-cytokine pathways are significantly over expressed in patients who achieve anemia response following CYT387 therapy. This further suggests a dominant immune component that underpins ineffective hematopoiesis in responding patients. On the basis of broad treatment-related changes in gene expression we suggest that an important component of CYT387's treatment effect is down regulation of these dysregulated pathways. Ongoing studies include validation of select gene targets which will be tested prospectively in future treatment protocols, as well as correlation of gene expression with circulating cytokine-chemokine levels.

    • wahoo not letting me post a link but you can search ASH + "Gene Expression Profiling" etc for a summary of the program.

      It's scheduled for Saturday @ 5:30
      an excerpt:

      Conclusions: The current preliminary analysis suggests that genes relevant to immune response-cytokine pathways are significantly over expressed in patients who achieve anemia response following CYT387 therapy. This further suggests a dominant immune component that underpins ineffective hematopoiesis in responding patients. On the basis of broad treatment-related changes in gene expression we suggest that an important component of CYT387's treatment effect is down regulation of these dysregulated pathways. Ongoing studies include validation of select gene targets which will be tested prospectively in future treatment protocols, as well as correlation of gene expression with circulating cytokine-chemokine levels.

    • I may be mistaken but the Gene Expression Profiling is an oral poster session today after 5:30??

      I would guess Dr. Pardanani will mention these facts in his Sunday presentation. Clearly...something is different in the structure of cyt387 compared to others and it is interesting that they, (ymi and mayo), are way ahead.....further than we all thought in discovering the differences....

      Gopher

      • 1 Reply to flgopherone
      • Will try posting this one more time.
        The 2nd program is scheduled for 5:30 today. Conclusion --
        The current preliminary analysis suggests that genes relevant to immune response-cytokine pathways are significantly over expressed in patients who achieve anemia response following CYT387 therapy. This further suggests a dominant immune component that underpins ineffective hematopoiesis in responding patients. On the basis of broad treatment-related changes in gene expression we suggest that an important component of CYT387's treatment effect is down regulation of these dysregulated pathways. Ongoing studies include validation of select gene targets which will be tested prospectively in future treatment protocols, as well as correlation of gene expression with circulating cytokine-chemokine levels.

    • The second presentation is a monster. That impact is so important that all of the Jakafi presentations together can't touch the importance of it.

      • 2 Replies to investormdpart2
      • graysonbarnes@rocketmail.com graysonbarnes Dec 8, 2012 5:47 PM Flag

        1751 Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response

        Program: Oral and Poster Abstracts
        Session: 635. Myeloproliferative Syndromes - Basic Science: Poster I
        Saturday, December 8, 2012, 5:30 PM-7:30 PM
        Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
        Animesh Pardanani, MBBS, PhD1, Rebecca R. Laborde, PhD1*, Terra L Lasho, MT, (ASCP)1*, Christy Finke, BS1*, Alexey A. Leontovich, PhD2* and Ayalew Tefferi, MD1
        1Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
        2Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN
        Background: JAK inhibitors have significant palliative benefit in myelofibrosis (MF), mainly in the form of improved constitutional symptoms and reduced splenomegaly. Preliminary data suggests that CYT387, a JAK-1/2 inhibitor, also has the ability to produce anemia responses (ASH Annual Meeting, 2011). In general, the mechanism(s) underlying treatment effects of JAK inhibitors remain unclear but likely represent a drug-specific balance between anti-clonal activity and modulation of immuno cellular-cytokine pathways. We conducted a gene expression profiling (GEP) study using primary cells from MF patients undergoing therapy with CYT387 followed by correlation with clinical data.

        Methods: Study subjects were enrolled in the Phase-1/2 study of CYT387 treatment in patients with primary (PMF), post-polycythemia vera (PPMF) or post-essential thrombocythemia (PTMF) myelofibrosis. Paired research samples were collected; the time points were pre-study and 12 weeks after commencing study treatment. PBMCs were purified from whole blood by Ficoll separation; RNA was isolated from this cell fraction for GEP analysis. Gene expression profiles were generated using Illumnia Human HT-12 v4 microarray. Pair wise analysis was conducted using the Wilcoxon signed-rank test with a p-value cutoff of 0.05 to generate lists of differentially expressed genes between assigned groups. Pathway analysis was conducted to identify relevant pathways enriched for differentially expressed genes. Comprehensive plasma cytokine profiling was performed using Multiplex Bead-Based Luminex technology (Invitrogen, Carlsbad, CA).
        Results: Seventeen patients were studied based on sample availability; 11 (65%) mere male with median age of 66 years (range 53-85). Twelve (71%) were JAK2V617F mutation positive and the DIPSS-plus risk categorization was 10 (59%) high and 7 (41%) intermediate-2. All patients were evaluable for anemia response; 14 (82%) were red cell transfusion dependent at study start. Nine (53%) patients achieved anemia response by IWG-MRT criteria; of these, 8 patients achieved transfusion independence (minimum non-transfused hemoglobin level of 8 g/dL maintained for at least 12 weeks) and 1 had a sustained 2 g/dL increase in hemoglobin level above baseline.
        The initial pair wise analysis to identify differential patterns of gene expression compared pre- and post-treatment groups (Figure 1A). This revealed a cluster of significantly (p

      • Which second presentation are you referring to? Thanks.

        Sentiment: Hold

 

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