2016 Earnings Summary
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On the right of this slide, you'll see the naive patients. So they have not been on treatment, so their sweat is stable. And as well, their FEV levels stay stable between screen and day minus 7 and baseline, than medication starts.
The next slide, so we have increased dose in SAPHIRA 2 after 2 weeks. So patient took first 62 milligrams bid during two weeks. And then 125 milligram bid in the second of week three and four. And we see that the exposure came in at the lower end of our expectations. That has been a bit unfortunate in SAPHIRA 2.
That meaning, so patients were a little bit under-dosed the first two weeks, who showed a low level of activity. And then the second half, they showed clear activity, but still suboptimal.
So in terms of FEV, which you see on this slide, you can see that in the ivacaftor pre-treated patients, we did not see a further decline. So we believe that's a sign of biological activity. If we would treat them optimally, you would want to see the 3% loss being restored. But take care, patients have only been for two weeks on the really active dose, and then we'll see it on the optimal dose probably.
And then on the right you'll see the ivacaftor naive patients. So for two out of three, we see a nice increase of around 4% to 5%. There's one patient which starts with a very low FEV so a percent of FEV of less than 40%. It's well known for this type of patient that they have a hard time in showing an FEV increase. So it's much harder in this type of patients to show a 5% to 10% FEV increase.
So we are pleased with this data. They clearly show that our compounds as well have an impact on the FEV. But we have to take care so a small study, a small number. But the trend is there that on FEV we have seen impact.
Next slide, we also did measure sweat chloride. There the same picture, so the first two weeks low level of activity, with only two out of five patients showing an increase, and then a little increase of 50 millimol per liters, which is the threshold for calling this a change of sweat chloride.
The second part of the study with increasing the dose, four out of five patients get to the [Indiscernible] as well. One patient gets to a high level 50 millimol change of sweat chloride. These are drops of sweat.
So I show the same picture, the low level of exposure in the first two weeks really caused effectively a suboptimal activity, three signs of activity. To get the full power of 1837, we should have included a higher dose, which will be part of the SAPHIRA 1.
And next slide please. So the conclusion for SAPHIRA 2 safety and the storability, the compound performed as we expected. So the typical side effects which we see in early clinical studies, but nothing to be worried. So our big goal, of course, is not to go ahead [ph]. We've always said that the SAPHIRA 1 shows better results compared to Kalydeco that we will develop 1837. So we have to wait for year-end data. So I can promise you those data will be there before yearend, and then we'll see how well it performs on mono therapy.
Our big goal is really the triple combo. And to that respect, we have 2451, 2222; which really have a once-a-day PK profile. And so by yearend we should as well have the Phase 1 data of 2737, and then showing us whether we can really go for the once-a-day compound with this triple combo, or whether it's going to be bid, because 2737 is a bid compound.
And then 1837 comes in the mix as well with more data, as part of the full SAPHIRA program. But so the choice hasn't been made yet. And we will decide that around year end.
Next slide, so moving forward, a triple brings us into a very intensive CF program. So these are the clinical studies only. So SAPHIRA on top with potency, with only patient evaluation. 2451 in Phase 1 as we speak, we've dosed cohorts this week. So it is moving on nicely. And 2222, Phase 1 completed, and we'll move into patient studies soon, as well as we speak, first as a mono therapy, and later we will add combo study data as well. And then 2737 starting Phase 1, as planned, in Q4.
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