Aptose Biosciences Inc (APTO)

[Tartiaboy]

Brian Druker has a library of AML plasma samples that he uses for in vitro IC50 evaluations of potential drug compounds. Years ago he evaluated the IC50s for Lux (806) in these AML plasma samples. In the trials the plasma level of Lux G1 has plateaued at approximately 1 microM per the recent reported data. If you look at Drukers data, approximately 15% of the AML in a panel of over 200 plasma samples had an IC50 at or over 1 micoM. To my knowledge Druker's library is a general collection of AML patient plasma samples-i.e. it is NOT SKEWED to the hard to treat r/r patients. On the other hand APTO targeting only hard to treat AML patients. My belief is that virtually all of the AML patients treated with G1 AML are in the category represented by the 15%. i.e. 1 microM G1 Lux is not enough. That is what we have seen in the scale up.
One approach is the new G3. If they can get the plasma level up to 4 or 5 microM, we may see some AML CRs. In the one patient that achieved 4-5 microM, we DID see a CR.

But here is why I am hammering on the combinations. Druker also did a assessment of Lux (806) IC50 in combinations with Venetoclax. He used approximately 95-100 AML plasma samples (hard to count them on the graph). ONLY TWO had an IC50 above 0.7 microM. i.e. if APTO had done the dose escalation of G1 in combination with Venetoclax we may have see many CRs.

The good news is that there are similar synergies expected with Tusp + venetoclax. That combination will initiate early next year. I am focused on that.