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YM BioSciences, Inc. Ordinary S Message Board

  • tundrasci tundrasci Mar 3, 2006 1:56 PM Flag

    April Abstract - TES

    Not certain if you have this one:

    Abstract Number: 5421
    Presentation Title: Preferential potentiation of paclitaxel and doxorubicin cytotoxicity in drug-resistant breast tumor cells by tesmilifene
    Presentation Start/End Time: Wednesday, Apr 05, 2006, 8:00 AM -12:00 PM
    Location: Exhibit Hall, Washington Convention Center
    Poster Section: 14
    Poster Board Number: 15
    Author Block: Stacey L. Hembruff, David J. Villeneuve, Amadeo M. Parissenti. Sudbury Regional Hospital, Sudbury, ON, Canada
    A phase III study of anthracycline-na�ve women with metastatic breast cancer by the National Cancer Institute of Canada Clinical Trials Group (MA.19) revealed that treatment of patients with doxorubicin in combination with N,N-Diethyl-2-[4-(Penylmethyl)Phenoxy]Ethanamine (tesmilifene) was superior to doxorubicin alone in terms of overall survival (P=0.021), with no difference seen in response rate or progression free survival (J. Clin. Oncol. 22: 269-276, 2004). One possible explanation for this observation may be that tesmilifene specifically increases the cytotoxicity of chemotherapy drugs only in rare drug-resistant cells, thus inhibiting the development of drug-resistant tumors over time. To assess this hypothesis, we examined in a clonogenic assay the effect of tesmilifene (at concentrations ranging from 0.1 to 6 μM) on the ability of doxorubicin or paclitaxel to kill wildtype MCF-7 breast tumor cells and isogenic MCF-7 cells resistant to doxorubicin or paclitaxel (MCF-7DOX and MCF-7TAX cells, respectively). Consistent with the above hypothesis, tesmilifene decreased the concentration at which 50% of MCF-7TAX cells were killed by paclitaxel (the IC50) in a dose-dependent manner by as much as 4-fold (at 6 μM tesmilifene), while having little effect or increasing the IC50 for paclitaxel in wildtype MCF-7 cells, even at the highest concentration of tesmilifene. Cross resistance to doxorubicin in MCF-7TAX cells was also reduced in a dose-dependent manner by as much as 4-fold by tesmilifene, while only slightly increasing the IC50 for doxorubicin in wildtype MCF-7 cells at the highest concentration of tesmilifene. The IC50 for doxorubicin was decreased by as much as 2.5-fold upon the addition of tesmilifene to MCF-7DOX cells (also in a dose-dependent manner), with little change in the IC50 for doxorubicin in wildtype cells. Since our MCF-7TAX cell line overexpresses P-glycoprotein (P-gp), while our MCF-7DOX cell line does not, it would appear that the effect of DPPE on the cytotoxicity of chemotherapy drugs in drug-resistant cells is not P-gp-specific, although this may be enhanced in P-gp-expressing cell lines. While accumulation of paclitaxel or doxorubicin was reduced in MCF-7TAX and MCF-7DOX cells, respectively, tesmilifene (at a 3 μM concentration) had no effect on the uptake of paclitaxel or doxorubicin into MCF-7, MCF-7TAX, and MCF-7DOX cells. Taken together, our data demonstrate that tesmilifene augments the cytotoxicity of paclitaxel and doxorubicin but only in drug-resistant cells through a mechanism unrelated to drug accumulation defects inherent in these cell lines.

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    • You can't compare the two companies. CTIC is run by an arrogant goon so egomaniacal almost half his board resigned rather than participate in his doomed effort to get Xyotax to approval in women. Doctors at scientific conferences openly laughed at the Xyotax trials. It was the worst kept secret in biotech those trials were going to fail.

      YM may have issues requiring caution, but it is not clearly a run-for-the-hills situation like CTIC. In fact, all the companies you mention (perhaps except for PTIE) have questionable management. YM doesn't merit inclusion in that gang. [It is always we are different from the rest until it isn't. I would not characterize any trials run by Dr. Langer from Fox-Chase as laughing stalks. But he wasn't overseeing who was admitted in the trials in Russia or Poland, was he?]

    • >>Weeks before the blowout in the Xyotax trials<<

      You can't compare the two companies. CTIC is run by an arrogant goon so egomaniacal almost half his board resigned rather than participate in his doomed effort to get Xyotax to approval in women. Doctors at scientific conferences openly laughed at the Xyotax trials. It was the worst kept secret in biotech those trials were going to fail.

      YM may have issues requiring caution, but it is not clearly a run-for-the-hills situation like CTIC. In fact, all the companies you mention (perhaps except for PTIE) have questionable management. YM doesn't merit inclusion in that gang.

      Another message in this thread suggested downside for YMI on a tesmilifene failure would be minimal because of AeroLEF and nimotuzumab. YMI without tesmilifene is worth about $2 in the eyes of wall street. We can all do math that tells us otherwise, but hedgies are buying this for tesmilifene not the other drugs.

    • "do you know there is a lifetime exposure limit for anthracyclins due to accumulative cardiotoxicities ?"


      I know. Also I know that in the MA-19 trial, dosing was cut short of target when BMS withdrew at an interim-look phase, and still there had been enough Tesm dosing to make a huge difference.

    • I don't understand why there is all this bashing of aqua. He is not one of those obnoxious shorts that makes senseless posts. Read his previous posts...he has plenty of valid points.

      There are so many bulls on this board that are completely oblivious to the risks of YMI in tes. Instead of telling aqua to leave, why don't you listen to the other side of the argument. And if you think there is no bear argument...then you are hopelessly blinded.

    • Is there a purpose to your constant postings? Are you the data savior? Exactly what do you claim your intentions and purpose are?? If you have raised questions about the MOA and or efficacy and that the Tes. trial may not be a slam dunk, fine. But to what end. You imply you are not an investor and that you go to multiple boards and do similar analysis. I assume since you have so much daytime time your regualr job is to trash various biotech microcaps which by definition are speculative and iffy. But I repeat, since you are so free with your insightful analysis, what the hell is your purpose. Why don't you explain that in as much detail. I'd be willing to bet substantial money you don't answer or if you do it is nonsense.

    • If the company was cheating, lying, etc as you claim the past trials would have ruled out the drug long ago. We would not have advanced to a pivital trial.

      Cover your short and move on.

    • Especially the women with cardiac conditions who cannot weather Avastin [and you are giving them the anthracyclins? do you know there is a lifetime exposure limit for anthracyclins due to accumulative cardiotoxicities]

      btw - those who doesn't believe my take have called my comments everything including false tales, half analysis, red herrings etc etc. That was before the data blowup. I've never heard from the same naysayers since, maybe they did get a total wipeout.

      We will count the number of herrings when the data is released, shall we.

      Just don't ever claim the company lie, cheat or scam you. It is you who have not noticed all warning signs even a blind bull can see.

    • aqua is probably the one who sold 5000 contracts of 7.5 Jul calls last friday

    • If Aqua is 100% correct, the stock will dip but the total market cap of this company isn't too high for nimo alone.

      Watch nimo.

      And the tesmilifene SPA and fast track status are still indicative that 75% of breast cancer patients may have help soon. Especially the women with cardiac conditions who cannot weather Avastin.

      I always enjoy hearing the bear side.

    • formerly_traderrnule_prophet formerly_traderrnule_prophet Mar 7, 2006 4:16 PM Flag

      Concur with you kwrnn.
      This guy aqua is one of two things
      a) short b) trying to get a lower entry price
      It is apparent that as one poster stated his analysis (or lack of complete review of the data) is 'merely a red herring' nothing more nothing less

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