Panna Sharma: I’ll take a first crack at that. In regards to the LP-300, we will not be doing any genomic based selection because that’s kind of already been done in many ways because these patients will have relapsed or stopped responding to TKI therapies. So they’re kind of self-selected already for that as never smokers. We will be taking liquid biopsy for these 90 patients. And those liquid biopsy results might give us some idea about potential surrogate markers of response or potentially some interesting signatures that correlate to improved response in certain types of patients. But we won’t know until we collect that, but that data will be very useful in future studies, potentially Phase 3 or to license the drug out. But for the current trial, one of the beauties of the trial is that we already have patients that have been genomically stratified because these are going to be TK failures largely.
In terms of the additional combinations, like with spironolactone, with PARP inhibitors, we definitely think the spironolactone seems to be a significant enhancement in the potency of 184 and perhaps 284, but definitely 184. And we can see ourselves using that as an additional arm in certain cancers where we may want to see a uptick in the potency, or maybe we may see in certain patient types a less than ideal therapeutic window or safety profile. So if you want to give less drug, but get a heightened response or the same response at the tolerated dose, then that’s where we could use spironolactone. But we see that as being introduced as an additional arm in the trial. In terms of PARP, we’re early on, but we think that we could actually mount some trials directly with PARP and compare it head to head against PARP alone.
Because as you know, PARP has got a couple billion dollars in sales in certain indications. We think in many of those indications, we can significantly improve the outcome. And I think, Kishor, you had some data on PARP on the approval and you want to share some of that with Michael.
Kishor Bhatia: PARP inhibitors have been approved for, for example, for prostate cancer. Clearly, focused on those prostate cancers that have mutations in BRCA or ATM. But after some time, several of these patients do develop resistance. So one part that also is that €“ A, the combination might delay this resistance, but in addition, if they become refractory, then perhaps LP-184 will still work on those. And there are toxicities associated with, of course, both LP-184 and PARP. And using a combination in a more strategic way to diminish those toxicities is another path that we have.
Michael King: If I can maybe summarize what I’ve heard, is it fair to say that you’ll need to get single agent PK/PD for your maybe recommended Phase 2 dose before you start adding things like spironolactone or adding to PARP.
Kishor Bhatia: At this time, that’s .
Michael King: Okay. So, the question I have on spironolactone €“ I can understand PARP, you could probably refer to data that’s in the public domain as far as what single agent activity should be from a PARP before you add 184 on top. Bu I’m just wondering, in the case of spironolactone, where it’s not thought of as an anti-neoplastic, how does one it €“ because when you do combination studies, the FDA is always interested in what does the agent add as a single agent? Do you have to do some studies showing that spironolactone no effect on tumors?
Kishor Bhatia: Yeah. Spironolactone is an FDA approved drug. So the safety profile and other things are known about it, those are the pharmacokinetics. We have already gathered data in vivo in animal models that the combination works and is more effective in certain context of certain tumors more effective than LP-184. So we believe that the data we have is sufficient for us to go to the FDA and design a study to use this combination.
