I see from the CC transcript that Infinity hasn't seen good activity in MM with IPI-504 as a single agent. This is a different tune from what was sung last year about IPI-504 in murine human tumor xenograft models of MM. Dr. Adams also notes that a combo with Velcade is the way for Infinity to fly there. But they have to get through more trials to determine dosing, so no timeline was given on when such combo trials might begin. Dr. Adams says they would prefer to stick to tumors in which single agent therapy would be viable, particularly those sporting "oncogene addiction," which is the dependence of the tumor on a single mutated protein for growth and survival. He said that GIST was one such cancer, and that there were several leukemias fitting that description, as well. Also many solid tumors, such as breast, prostate, lung, renal, and melanoma. If they are able to get good activity as a single agent in these tumors, that would be great.
DMAG is also in PI for solid tumors, and that is still recruiting; we don't know what types of patients are being enrolled at this time. I'm willing to bet they are looking at the same cancers that Infinity is, because the drugs have the same MOA. In their PI for hematologic malignancies, though, Kosan saw a couple of complete responses in refractory AML patients. I assume Infinity is looking at AML, too.
So it's a neck and neck horse race for DMAG and IPI-504, but again, 17-AAG works well enough for hematologic cancers that the pivotal trial with Velcade is starting next year. Way ahead of Infinity in that respect, and while I don't like 17-AAG by itself because of it's solubility and half life issues, this combo looks like a winner to me. Second to market is often a good place to be if you have the better drug, but will IPI-504 be second or third (which is not so good)? It'll be some time before we know, and some time before we know if it is any better than DMAG. Potency is similar. Kosan claims 3-5 times more potency than 17-AAG, while Infinity claims 2 times more potency than 17-AAG for IPI-504.
Both companies are working on an oral formulation, and the that's neck and neck in the early stages, too, though Kosan is already in PI with its version. I gather the oral IPI-504 is not in humans trials yet.
Question: did we know before the recent CC that IPI-504 as monotherapy in MM had whiffed in humans? I was thinking that revelation was responsible for the recent splut of the share price. But the CC was on the 14th, and while the 15th was weak, it was the 16th where we really saw the dive and the volume. Maybe the 16th was when ASH abstracts became available?
I went and looked at those abstracts, I didn't see anything that wasn't alluded to in the CC. Kosan's patient were all AML, but one (CML). So we can't really compare responses. For whatever reason, DMAG was given at noticeably lower doses than was IPI-504, but on similar dosing schedules. I have seen that IPI-504 is 4000 times more soluble than 17-AAG, but have not seen a similar metric for DMAG. It sounds as though DMAG is more potent, and that MIGHT explain the difference if the solubility is comparable. I have seen reference to DMAG having twice the oral bioavailability of 17-AAG.
Other advantages of DMAG over 17-AAG (such as fewer unfriendly metabolites and suitability for "metronomic dosing schedules") can be found here:
clincancerres.aacrjournals.org
Disclosure, if I didn't give it already: my Mom owns both of these.
Cheers, Tuck |
