Biotech Values

[poorgradstudent]

PI3K:

That program seems to be about 18 months behind, so it would take a pretty good flub by TG lose their lead.

Definitely. I'm not suggesting Incyte is ahead by any means. Rather, the tangible advantage TGTX enjoys right now is their long development lead on competitors. I think it much more important to focus on that element rather than the safety element.

At this year's AACR, TG pointed to preservation of Treg function versus idelasib and duvelisib (which just flamed out) as an explanation for the lack of hepatotoxicity versus those two. But they didn't point to the responsible moiety. Has Incyte found a different way?

At a recent presentation, Incyte suggested a specific part of the chemical structure was the culprit and they engineered it out of the new generation compound. Perhaps that has downstream effects consistent with TG's hypothesis.

And how would you debate the data re AEs? So far, seems pretty clear per my research; the short case is that it's early and the bad AEs will show up later, or that TG is underdosing and will suffer on the efficacy side.

I think it's reasonable to assume that the TG drug is currently looking more benign on the AE front. But in a drug dosed at ~1 g amounts, I wouldn't be surprised if they're balancing an efficacy vs AE consideration above and beyond what companies normally have to do.

Extreme case is an old drug like nimotuzumab, the EGF-R antibody without rash that was clearly underdosed / low affinity and suffered on the efficacy front.


I think we're in agreement that the marketed PI3K drugs have shortcomings. I'm still somewhat ambivalent about this class of drugs. My suspicion is that they will end up being complementary in very specific combinations in very specific indications.