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Exelixis, Inc. Message Board

  • wilderguide wilderguide Jul 21, 2013 12:46 AM Flag

    Not quite off-topic, and perhaps spot on topic...

    Most of you have already figured out that I am also invested in SNTA. This has less less to do with any particular affinity for that biotech than it has to do with my growing interest in HSP90i. I also own INFI (retaspimycin) and PFE (SNX-5422)...and am increasingly aware that EXEL may be sitting on a very valuable asset in orally bio available XL-888. Though- I must admit - at this juncture, I feel IV - administered ganetespib may have the edge given the current landscape, stage of development, and AE profile.
    But I ramble. One of the most appreciable aspects of SNTA's corporate presentation is that it is regularly updated, and the July 2013 update has included a chart reference to Cabozantinib that I do not quite understand. If you would, take a look at slide 44 of 45. It's titled "Recurrance-free interval in 20/65. USPIs reviewed". Cabo is highlighted as one of the 20 at review. Check out the lower LH corner of the chart.
    Any comments greatly appreciated.
    Ernie...there are some trial endeavors proposed in this recent SNTA corporate update that might entice your bio-curiosity. Great experimental trial rationales, and it appears Ganetespib may further inspire some IST/ NIH financial backing in combo setting. I wish EXEL would put together a "go-to" presentation site like this one - with regular updates, and planned trial rationales. Finding what you need at one regularly updated locale is a great plus.
    One stop to speak.

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    • Wilderguide, The initial HSP90 inhibitors fell out of favor due to ocular and liver toxicity issues. Ganetespib is a next generation HSP90 inhibitor which doesn't have such toxicity issues, but I believe that Retaspimycin from INFI still does. As far as EXEL and XL-888, it would be very useful if we could find out what its toxicity profile is.

    • wilder... not sure if you have seen this but you might want to google... Dr. Suresh Ramalingam on Hsp90 Inhibition With Ganetespib

    • UAPI=United States product insert

      They reviewed the FDA approved indications for several oncology drugs and noted that some of them have modifiers that pre-select for less aggressive disease by specifying intervals free from progression or similar criteria. In the case of Comet, I think they got it wrong. The EXAM trial required a more aggressive disease by making progression within 14 months a requirement. It's relevant to SNTA because they noted that G is most effective in less aggressive disease.

      • 1 Reply to erniewerner
      • Ernie, right on target as usual. As far as SNTA and their Galaxy 1 phase II trial in 2nd line NSCLC, I will point out that Ganetespib also shows efficacy in overall adeno-carninoma. It is just that is appears far more effective in the less aggressive cases, and that is the group SNTA has designed the phase III trial for to maximize chances for approval. Ganetespib was also quite effective in delaying the appearance of new metastatic lesions, which might explain why it is more effective in the initially less aggressive cases. One other tid-bit that came out from the 2nd-lin NSCLC trials is that Ganetespib appears more effective in women than men. I surmise this is related to female hormonal effects on cancer progression as estrogen receptors are one of the major clients of HSP90, and therefore most affected by HSP90 inhibitors. This might bode very well for the Ganetespib phase II breast cancer trial in progress.

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