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Incyte Corporation Message Board

  • maddison3 maddison3 Jun 2, 2013 10:17 AM Flag

    Thoughts on ASCO announcement

    I think this is big, big news....Just think if it works in P3 we are sitting on a real goldmine. I know TJ that is years away! Just think you probably have 3 more years to infest this MB!

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    • What we KNOW is that this is a legitimate drug candidate. Oral dosing can get the drug to effective levels and the toxicity isn't so high as to create a question as to whether dosing will be possible. The mention of long duration of treatment (which would have been stopped upon death or substantial progression) is encouraging. If all goes well, an introduction might be 5-6 years off, by which time Incyte could probably finance it. Make a nice closing number for Dr Paul.

    • 360 has been working big time for Jeff John in a metastatic melanoma P2 trial in combination with BMY's drug Yervoy. I look forward to the drug working as a monotherapy in other disease settings as well such as ovarian cancer where it will be up against Tamoxifen in a P2 trial. It's mode of action is described nicely in the following PubMed abstract from 2010:
      Malignant tumors arise, in part, because the immune system does not adequately recognize and destroy them. Expression of indoleamine-2,3-dioxygenase (IDO; IDO1), a rate-limiting enzyme in the catabolism of tryptophan into kynurenine, contributes to this immune evasion. Here we describe the effects of systemic IDO inhibition using orally active hydroxyamidine small molecule inhibitors. A single dose of INCB023843 or INCB024360 results in efficient and durable suppression of Ido1 activity in the plasma of treated mice and dogs, the former to levels seen in Ido1-deficient mice. Hydroxyamidines potently suppress tryptophan metabolism in vitro in CT26 colon carcinoma and PAN02 pancreatic carcinoma cells and in vivo in tumors and their draining lymph nodes. Repeated administration of these IDO1 inhibitors impedes tumor growth in a dose- and lymphocyte-dependent fashion and is well tolerated in efficacy and preclinical toxicology studies. Substantiating the fundamental role of tumor cell-derived IDO expression, hydroxyamidines control the growth of IDO-expressing tumors in Ido1-deficient mice. These activities can be attributed, at least partially, to the increased immunoreactivity of lymphocytes found in tumors and their draining lymph nodes and to the reduction in tumor-associated regulatory T cells. INCB024360, a potent IDO1 inhibitor with desirable pharmaceutical properties, is poised to start clinical trials in cancer patients.

      Sentiment: Buy

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