Is Aptose a Good Bet Going Into EHA21 Presentations?
Aptose has some impactful #EHA21 presentations coming this week for its lead drug, a Btk and FLT3 kinase inhibitor called #Luxeptinib (See BPIQ detailed article on this topic HERE). So the question for investors is whether #APTO is a good bet going into these presentations. Here are some bull and bear arguments:
Bull Case:
- APTO has been ramping up its dose escalation studies from very low dosing levels and is now at a dose (750 mg twice per day) in the B cell cancers trial that is high enough (2uM plasma concentrations at 750 mg dose (https://bit.ly/3iwmp7X)) that the efficacy signal should come through, especially considering that Btk is a well-validated target;
- Leading indicators of clinical activity including in vivo kinase inhibition, lymphocytosis, and some tumor reductions have been observed, even if many tumor reductions to the extent needed to be characterized as a responses have not been observed;
- This situation is very analogous to ARQL and ARQL 531 from a few years ago where investors started to get worried about no/low efficacy signal of clinical responses although some early indicators were present; Eventually once the dosing was a high enough the efficacy signal came through strongly (needed 45 mg once daily - over 250 nM plasma concentration, despite an IC50 for Btk of 0.85 nM (~10X more potent than CG806 See FIG. 1 below);
- APTO also has the AML trial related more to Luxeptinib's FLT3 inhibition, which gives it a unique activity profile (See FIG. 2 below for side by side kinase maps of Luexeptinib and ARQL 531) giving it a second "shot on goal" for this asset, and the initial cohort there showed a clinical response in its first dosing and early reads.
Bear Case:
- Luxeptinib's doses have been at a level where kinase inhibition has occurred and should be showing more clinical responses already;
- Luxeptinib at 450 mg twice daily should have showed clinical activity already, given that LOXO-305 shows clinical activity at 200 mg daily, and Luxeptinib has similar IC50s to LOXO-305;
- This appears similar to Vecabrutinib, which showed kinase inhibition but with continued increasing dosing never showed clinical activity to the point of a confirmed response.
Amp's Viewpoint:
What is our Amp view on this one? Although we think it is a close call because Luxeptinib should have shown more clinical activity at the 450 mg dosing, we are in the Bull camp on this one. We own APTO in all of our accounts currently, and will continue to hold go into this data. Vecabrutinib appeared to show more safety issues, especially as doses increased, and never showed much clinical activity, despite in vivo kinase inhibition. Our recollection of ARQL 531's clinical trial history, was that there were some early clinical activity in a few patients that then became profound once they hit a high enough dose and those became deeper over time. Plus, we like Luxeptinib's AML early data, which gives a whole new potential success route even if the B cell data does not play out to be competitive with other Btk inhibitors. Finally, at a market cap under $500M, from a comparative standpoint to ARQL, APTO seems to have a good amount of upside if the data is positive.
It will be interesting to see if APTO's corporate update tomorrow is a joyous occasion, or a company refocusing event. Of course, mixed data (e.g. still underperforming B cell data but better AML data), might bring a mixed emotion call. We are betting on the positive momentum from their Q4 call in March with additional clinical data, drives more positive news on tomorrow's call.
What's your view on this one? Let us know in the comment section below.
FIG. 1 IC50s of competitive non-covalent BTK inhibitors (and Ibrutinib).
FIG. 2 CG806 (left/top) vs. ARQL 531 kinase maps
#luxeptinib #APTO #ARQL #ARQL531 #CG806 #LOXO305
#Vecabrutinib #CLL #AML