RE:RE:RE:RE:RE:RE:RE:RE:TH-1902 pause is no reason to blame managementOne problem we have is that we have little to no data. We just keep guessing.
But I do know this as a fact. My wife had a large cluster of tumors on her right upper flank. It was her main source of pain. Soon after she went on the TH1902 trial the pain went away and that tumor shrank. By the time she passed that cluster which had been the size of my fist, completely dissappeared. These were cystic tumors.
Ovarian cancer is a painful death but my wife passed peacefuly and without pain. She did not even need to take any morphine or any other painkillers.
Some ovarian cancer patients have something called carcinomatosis. Many small tumors lining the peritoneal. My wife was down below 40kg when she passed and the nodules were clearly visible on her abdomen. These nodules did not shrink. What was different between these tumors compared to the one on her upper right flank?
I am not looking for answers. Just trying to give you a small data point. I am sure there are many data points avaiable to Thera but someone would need to make sense of any patterns if they exist.
qwerty22 wrote: Well if we are genuinely at a reset moment then Jfm bleating on about this finally starts to make some sense. I'm still not convinced THTX have the expertise or setup at UQAM for this. It would be an expensive contracted out project so whether it works from a business perspective is debatable. It would also mean going right back to the R&D stage.
The small amount of evidence we have says degradation of the drug isn't the problem. Why it's hitting Sortilin in healthy cells and not in tumours in humans seems like the biggest question here. Isotopes would confirm that is exactly what is happening but they might not get you the "why" and it would be a long road to get there.
It seems to me there is a possibility that it's more to do with the peptide than the payload. That the peptide needs to be tweaked so that it's doing it's job within the tumour better. Again that takes us back to the start and a focus on R&D.
Unless they are holding on to data that gives clues here I don't see any quick answers. Changing the dose looks like more guesswork unless they have convincing data to support it.
I agree with Jfm that trying different chemo drugs doesn't seem to make sense with the present scenario but for different reasons.
jfm1330 wrote: The problem with chemo drugs like docetaxel, doxorubicin or SN38, is that you need selective cleavage of the linker inside the cells. That means part of it will cleave outside the cells, in the bloodstream. One of the big advantage of radioisotopes, is that cleavage from linker is not needed, in fact, it needs to be completely avoided. All you need is PDC bonding with the receptor and internalization. If TH19P01 can do that, this part of the concept works. The other part of the concept would be related to sortilin expression throughout the human body and tumors. What is the distribution of sortilin within the human body and how much of the PDC is it catching? This is key for toxicity and Ga68 would allow to measure that. Ga68 could also allow to select only the right patient that are overexpressing enough sortilin on the cancer cells.
LouisW wrote: Maybe SN38 is doable? I guess they already have some data. jfm1330 wrote:
TH1902 TH19P01 PDC Aeterna Zentaris PDCAEZS-108 Zoptrex PDC Thera Ib TH1902 TH19P01 “” PDC PDC ADC Lutathera PluvictoLu177-Dotatate Lu177-PSMA Lu177 DOTA Pluvicto “”Thera TH19P01 DOTA TH19P01 Lu177 Ga68 Ga68 “” Ga68 Lu177 I Ga68 Lu177 Lu177 TH19P01 DOTA-Lu177 DOTA-Ga68 ADC