Biotech Values

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GERN - myelosuppression/safety...

So let's move on to the -- let's move on quickly to the safety, the appropriate safety. So here, we wanted to make sure we were as up to date as possible as I told you. We don't have the data from the patient from 23 through 33. So we are going to just simply repeat Dr. Tefferi's slides because I think they're very well done and quite illustrative. So this is Cohort A and is equal to 11, Cohort B as before. Now what we are going to do as he described, we were going to do a Cohort C which is going to be weekly, but after seeing the myelosuppression that occurred after weekly dosing, this was not a difficult decision. Dr. Tefferi made it but we were in complete agreement that this was -- that these patients could not be treated weekly. And so these patients were reallocated to either Cohort A or Cohort B. The patients who got into Cohort A were patients that had mutations in particular splices on mutations that might have suggested that they would be more sensitive. I'm not sure if that's true or not but it was a theory at the time and these patients were thought not to be as sensitive.

You saw this. This is the patient disposition. There's really nothing new to talk about. It's collated to slightly different way, but there have been no additional deaths, no additional transformations. We're unaware of any other changes, a lack of response and this is more updated that you can't pick and tie, guys. This is a more recent data set because he has access to those data. These are all of the grade 3 for non-hematologic adverse event that he showed today. He commented that these were not attributable to the drug in his view and these are the treatment related myelosuppressive toxicities and it ticks up with the picture that we've seen over and over again. I will tell you right now most hematologists who treat these disorders do not worry too much about grade 3, but they do worry about grade 4. And I think this is the very important finding in this and is equal to 33. The patients in the B -- group B treatment paradigm have clearly a higher grade 4 thrombocytopenia and neutropenia than the patients in grade 1 where there was no grade 4 thrombocytopenia and no grade 4, only 1 patients with grade 4 neutropenia. So this has certainly given us these observations that myelosuppression is principal dose-limiting toxicity. We think it's a theory that it's on-target toxicity due to effects on progenitor cells. I think most of the academics believe that to be the case. It's clearly manageable through dose hold rules and dose modifications. And to mitigate against the risk of severe persistent cytopenias, the Mayo Clinic protocol has been amended to raise the hematologic thresholds for retreatment and include more stringent monitoring and dose adjustment criteria. And the non-hematologic adverse effects have been generally not very much to write home about. So this -- these are the conclusion. We just simply reiterate the efficacy and safety conclusions. And so I think that I will end there, and we will open the floor to questions.