jfm1330 wrote: Sorry SPCEO, your working definition of proof of concept is impossible. With TH1902, as it is, they cannot see if it goes inside the cells and even less if it's pushed out of cells if it would have entered in. That's why I would want a version of the PDC coupled to Ga68.
I should have mentioned earlier that I had sent that info to Christian a long time ago as you requested when you first brought it up, so if he read my e-mail his is aware of it. With that tool you would be able to see the PDC distribution in the human body, in which organ, tissue and tumor it is internalized, and to which concentration. But TH1902 with docetaxel cannot be traced in that manner. All that to say that the only way to have a proof of concept is through efficacy. If docetaxel alone is no longer efficacious on a patient, but given through TH1902 it is. It is the indirect proof that it goes inside the cells in a different way and in higher concentrations.
It seems to me that there is a good chance patient #2 has seen that. That being said, pharmacokinetic data of TH1902 in the bloodstream over time, after injection, can give hints about proof of concept. The PK profile of a patient with a heavy sortilin burden (high sortilin expression on tumors and high tumor burden) should be different from the PK profile of TH1902 in a patient with low sortilin burden, for the same dose of TH1902 injected. This can give a good hint, but not a proof of concept per se.
I think we can conclude safely that they have such PK data in hand but we cannot know for sure what that data says - right?. Also, patient #2 cannot be considered a proof of concept because he or she got four cycles of TH1902, including three under the MTD of docetaxel alone, and we don't know what happen after the cycle at 300 mg/m2. Maybe he had stable disease during that time, and that's why he continued. But stable disease on one patient is not a proof of efficacy, so not a proof of concept.
Why would stabilizing the disease not be proof of concept? If it is stabilizing the growth of the tumor, it must be having an impact. Also, would a patient remain on an experimental drug for that many cycles if there was not benefit being shown? So, maybe they have hints of proof of concept, or real proof of concept throug efficacy, but without confirmed tumor regression, ideally reaching partial response status, this is just speculation.
I imagine they could get a partial response in phase 1a but since the trial is not designed for that, TH needs to get lucky. Given that they revealed patient #2 to us, that they are busy planning on an expnded phase 1b, that they hired a siRNA scientist and are also studying SN 38, it sure seems like they know they have something already.Until they publish their data, nothing can taken as a fact. That's why it's frustrating to follow. Hopefully, they will give us something reassuring in the next Q1 call in three weeks.
Any idea of how long it might take TH to work on all the data they have collected in the phase 1a before they say something official? SPCEO1 wrote: Now, I know our scientists here are going to remain on edge until they receive official confirmation from TH whenever they release the phase 1a results, but I believe they have already effectively told us they have at least achieved proof of concept by sharing that info on patient #2 in the recent corporate presentation. My guess that was the whole point of putting out a new presentation - to calm everyone's nerves about this and encourage us that the future should be very interesting. My working definition of proof of concept is that they have seen the drug enter the cancer cells and not get pushed back out before they can start damaging those cells. Given how many cycles patient #2 had, they may have also seen actual signs of efficacy. If patient #2 did not show some signs of efficacy, that would actually be a bit disapointing given how long they were on the drug (I know, most of the doses this patient recieved were low but given that the drug is supposed to concentrate in cancer cells even low doses should be beneficial as indicated in the preclinical work).