RE:RE:RE:More on the Meeting with Management All rodent models are bad on this front but the mouse R&Dwork is probably the least useful. Probably a little better is the rat toxicology work but they haven't yet published the toxicology data. From memory Paul did say early on that in the rat work they reached DLT at 3x equivalent dose in the rats.
What we know is at 420 dose they got what we might call unacceptable toxicities, they didn't quite reach DLT (they stopped before then). 420 dose is 1.8x docetaxel equivalent dose.
So
Pre-clinical in rats DLT at 3x equivalent dose.
Clinical in humans (not quite) DLT at 1.8x equivalent dose.
You can decide for yourself whether that's a pretty good match. My view is not too bad given a human can tell you they have blurred vision or numbness and a rat can't. I read a paper a while back that rodent toxicology studies match ph1 data about 25% of the time.
Going back to whether what they told SPCEO clinical was a match to the preclinical data or a match to their expectations that flowed from that preclinical data. I'd say 1.8x versus 3x easily falls inside expectations rather than matching the actual data.
jfm1330 wrote: I would add that what Marsolais said about phase Ia matching pretty well with preclinical data is a bit strange from the outside, because from what we know, it does not match at all with their previous claim that on mice they could achieve three time the MTD of docetaxel. At 1.3 times the MTD on humans as the likely phase Ib dose, they are very far from matching three time the MTD. That does not mean the concept does not work, it more likely means that a nude mice is not an advanced human cancer patient.
jfm1330 wrote: Remember that if TH1902 works to some extent, it would only be the first step with SORT1+. Many other PDCs could emerge from it with a proof of concept, and it is likely that a more potent PDC is possible with a better cytotoxic drug than docetaxel. With docetaxel, they went with the well known thing. Not a bad way to approach it, but by no means the best cytotoxic drug on paper. With a proof of concept, the value switch to the platform, not only TH1902. That's the way a potential big pharma buyer would see it, at least, that's the way Thera would have to sell it.
SPCEO1 wrote: Will TH-1902 get that BTD because it is shown to be highly effective and safe? Or will it just be another decent cancer drug among many others? Time will tell, but TH-1902 definitely has a chance to be something special and we will likely know more about those chances before the year is over.
I will have more later.