Wino115 wrote: I guess I should have been clearer. I've been trying to look at efficacy in the completely opposite direction since we know they have said nothing at this point. In other words, if we try to prove it is ineffective within the confines of what data has been released then we can narrow down the issues causing that ineffectiveness a bit and assess the probabilities of those knowing some data points around what they have shown to work in human tumor cells, the safety data, and what they haven't discussed. So it's inferring something around efficacy by proving non-efficacy.
The explanation around non-efficacy or limited efficacy can be argued from what we know since the data points are limited around that. As we have pointed out, there are perfectly valid explanations around it being ineffective. But based on the fact the massive drug dose has not caused any limitations or killed anyone that we know of, you have to guess what is happening to the chemo bomb in human bodies. If you can exclude some of those options based on the safety data, you are left with fewer choices as to what is happening to it. If you combine that with their statement that from all they have seen it has been consistent with the preclinical work, it narrows it even more. From that point we can each infer what we want.
But it leaves only 3-4 alternative explanations like it is being quickly flushed down the toilet and not doing much (yet we know it releases since someone had some mild neutropenia), it hanging around the tumor microenvironment (but that's basically what taxol normally does so maybe we are just another version. But at twice the dose, we would be seeing huge problems, yet we are not), the target not being found in abundance or receiving it (CMO said they have done the assay staining in the QA of last call, so they know the answer to one of those questions. We don't know this answer). So if none of the 3 or 4 explanations or what is happening to all that taxol conforms to the safety data and the few parts of the pre clinical that may be what they are referring to as "the what they expected to see", then it's hard to anti-thesis given the huge dose and the fact they would have probably had to already tell us the targeting is not working, it's degrading, and we see in the PK data this whole PDC is NOT working like in preclinical.
In other words, to believe ineffectiveness, you need an explanation around the actual data and statements, that's the other way to change your probabilities around an inferred effectiveness. Try to explain the other conclusions and have it conform to lack of SAE, no death, and seeing things similar to pre clinical (I only take that to mean where there is Sortilin, it finds it, attaches. Not that it necessarily internalizes). It's very hard to support the anti-thesis too. So.....?
palinc2000 wrote: I thought it was clear that my comment on Efficacy was exclusively related to data on Efficacy during Phase 1 ,,,,I dont know of a single data ,Do you ?
Of course there was efficacy during the pre clinical studies ,,,Otherwise they would not have initiated a Phase 1
Wino115 wrote: i wouldn't say zero data on efficacy. A lot of the pre clinical data is helpful, even if in non human hosts. I am fully on board with the fact we have no human data at all around efficacy and the pre clinical needs to be validated. So I don't disagree with you Palinc. I've always been in the hard data in humans camp for our valuation step function jump.
I would just revert back to my other post that we are now seeing an almost deadly amount of docetaxol being injected in to patients now, or at least a dose that in humans should cause all sorts of alarms to go off. We have data that no alarms are going off yet, just one SAE grade 2. We should probably be seeing the terrible SAE 5 at 2x dose level. So taxol is going somewhere "safe" and nor floating and harming organs.
The second data point would be in human xenographs of tumor cells, the peptide did internalize and release and shrink human tumor cells grafted to mice and rats. This could justify Sortilin targeting working, Sortilin internalization working on a human cell, and taxol doing its thin in the human tumor cell. We still need to see all this in human tumors in humans. But we could say what they saw pre clinical conforms to why they haven't killed anyone yet with that massive toxic chemo bombshell floating around. If we don't believe in efficacy we need to explain why the peptide didn't target right, why Sortilin didn't overexpression or was a valid target, why the linker failed, why taxol failed, and where the taxol went.
I think we've concluded it could be a case of it rapidly being flushed down the toilet or it just hanging around the receptor and not getting chemo in effectively. So if that happened, it is not what was seen in the human xenographs and it would mean their statement (data) that "...what we are seeing is similar to the pre clinical work..." would be highly misleading. In fact,mit would be criminally misleading for them to say that if either of our negative scenarios above were in fact the explanation.
So in a way, putting all those pieces together and ruling out explanations that don't conform to their statement that it's similar to preclinical is the biggest hint.
palinc2000 wrote:
We have zero scientific data on Efficacy but we now have 4 fantastic hints
1- The smiling KOL s during the Kol Event
2- Some kind of a retainer paid to a retired doctor with a great track record
3- Chinese sniffing around
4/ Paul is extremely excited on Phase 1
Did I miss anything on Efficacy?
I wish
SPCEO1 wrote: Glad to see you back! I hope your health is not causing you any problems.
I think the hiring of him at this time is likely the biggest hint we have yet that good thigs are happening on the TH-1902 front. THTX already knows enough from the phase 1a trial to not bring him on if it was going to be a dud. While we may still not see any signs of efficacy in phase 1a, THTX likely knows the chances of seeing that in phase 1b are pretty good as they would not bring him on if they already knew the cancer program was going nowhere.
While the analysts have not yet figured out that something positive is likely happening with TH-1902, the addition of Dr. Rothenberg and the Chinese sniffing around THTX looking for a partnership deal are indications the industry has started to figure it out.
jfm1330 wrote: Oncology is going so bad that they just hired an expert advisor...
https://www.theratech.com/about/scientific-consultants-and-advisors