Wheels Up

$qure $clpt Bye bye Warden Capital Q3 2026 Letter Says no thanks to @mahesh_shenai theory of Uniqure manipulating the data with proof. The same paper also says no thanks to placebo on tfc. Keep up the good work Mr Neurosurgeon with your odd and baseless theories. I guess they manipulated it also? “However, dropouts progressed faster according to some end points (eFigure 4), which could influence later observations and potentially explain the slightly slower progression observed in some end points, particularly in the cUHDRS score (Figure 4E).” Warden capital thoughts And speaking of drags, the biggest weakness this quarter came from Uniqure, which dropped significantly on a bit less clean than ideal 4 year results6. Much ink has been shed on this elsewhere, but my quick view is that the 4 year data is actually quite good in an absolute sense and in my view removes some of the tail risks on the drug approach not working longer term7. The trial did miss statistical significance on its 4 year target indication of cUHDRS, with 44% slowing but did hit statistical significance on the 4 year TFC with 61% slowing (these are two different ways to measure disease progression). The reason for the miss though was not the patients rate of decline accelerating significantly, but instead the natural history comparator looking much better making the slowing look relatively smaller. This appears to be very likely due to the sickest patients dropping out of the natural history control group as it becomes more difficult to travel to the testing centers and take the tests, which makes the natural control group look better than a typical patient pool.8 This isn’t just random speculation, we actually have excellent data to support just this conclusion from Roche’s failed Huntington’s trial. Roche made the data available and several scientists wrote a good paper which showed in detail how the patients who dropped out of the trial were progressing 50% faster than those who stayed, which made the end year readings look artificially better than the full patient pool, because the worst patients dropped out. Link to the paper is here, but what is really interesting are the supplements which you’ll need to download separately. So I would say my confidence this drug works is pretty high now. However I do not know what the FDA will do & there is definitely some risk they ask for a phase 3 trial, which isn’t the end of the world but would likely hit the stock price. But on the whole I would lean towards FDA granting approval next year as is with a confirmatory trial. This is for several reasons - the 3 year data is good, which is the basis of their submission (and indeed it got better in the recent release with more patients hitting 3 years), I think the FDA will understand this drop out issue, and most importantly, the FDA seems to prefer TFC as a measure of disease progression anyways, as this is what they are going to require the confirmatory trial’s endpoint would be. It would be strange if the FDA decided TFC is the proper end point, but then didn’t approve when the 4 year TFC was very good. But you never know in bioland! Original paper neurology.org/doi/10.1212/WN… @Christina4HD @laurencurehd @Tim_Corr @peter_mantas