RE:RE:RE:Not surprisingAt this time it is pointless to rely on preclinical data in order to find some releif. We are left in complete darkness about the data they have that would bring more clarity on the validity of the concept behind TH1902 in human patients.
As I said a few days ago here, I had my second of two treatments with Lu177-Dotatate, my eigth treatment since 2017. So I asked my doctor to show me the scans to have a clear idea of where I am at in comparison to five years ago. I wanted to see the progression of the metastases. He showed me that. I also asked him if my tumors were catching a lot of the PDC. He told me they were catching a lot of it and in order to illustrate that, he showed me other organs catching the PDC and said to me, see, your tumors are darker than the spleen or kidneys, this shows that they are catching a lot of the PDC since spleen and kidneys are overexpressing the somatostatin receptors. He also showed me other organs catching much less and some, nothing at all.
My point is that it was possible to see where this Lu177-Dotatate is internalized by the cells in tumors but in normal tissue. And it's really internalization, because the scans are made three days after the injection of the drug. So three days after injection, the beta radiation is still there in tumors and some organs. With TH1902 we have none of that, we are not even sure that every patient is overexpressing the targeted receptors on their tumors. Also, with radiation there is no resistance and radiation from one cell can affect neighboring cells. With docetaxel it's another story, many advanced patients are resistant to it. The idea was to allow a higher dose to enter the cells, but now they look at reducing the dose. So this potential advantage will also go away if it ever existed.
All that to say that no pre-screening for sortilin overexpression and possible docetaxel resistance are two factors lowering the potential rata of success from the beginning. So maybe a good percentage of the patients enrolled were not good for this treatment. Add the side effect on very ill patients. You end up in a position with not much power to show efficacy. And now with lower and more frequent dosing, they will aim more at stable diseases than clear objective responses that would allow a fast approval.