Aptose Biosciences Inc (APTO)

[Tartiaboy]

Ivosidenib and olutasidenib target various isoforms of IDH1 and will compete in a relatively small market. Both cause differentiation syndrome. Ivo causes QT elongation and Olut causes liver toxicity (both manageable). Tusp and Lux are NOT targeting the IDH1/2 enzymes. Never-the-less Tusp seems to be active against at least some IDH2 patients and possibly IDH1 patients. Lux has shown high sensitivity of IDH1mut versus wild-type in vitro. TUSP and LUX are broad multi-kinase inhibitors that individually hit many proven AML targets. They do not directly inhibit IDH 1 or 2, but they may be indifferent to these mutations in efficacy especially in first and second line use. If TUSP is successful for first line use it will not compete with any individual IDH inhibitor but it may dramatically reduce their need.

I think that the ability of TUSP and LUX (eventually) to inhibit AML cells with TP53 loss of function and RAS activation are the most significant breakthroughs. But both drugs do much more than that.