Looking a second time the presentationI started viewing the presentation a second time with the possibility to stop it and replay some interesting parts. The answer about the difference between ADC and PDC is interesting. Beliveau says that many ADC are not internalized inside the cancer cells, or if they are it is a much slower process. He also adds that most of the cytotoxic agent are then released outside the cance cell and need to diffuse inside of the cancer cell passively. He said that with TH1902 they see the induction of apoptosis (process of cell death) within a couple of hours, while with ADC, apoptosis is induced in tens of hours. On that, Marsolais added that because of that, they need to use much more toxic agent with ADC, compared with docetaxel. Also, just to see the smiles on the face of the three guys when asked if TH1902 would worked better with more advanced cancers expressing more of the sortilin receptors. Go back and look at the smiles. It says it all.
Beliveau said he thinks it is the only drug targeting the sortilin receptor and that he thinks it will work because of the nature of the sortilin receptor. He meant by that the fact that it is a receptor dedicated to import/export of large molecules inside or outside the cells, so it is the best possible target for a PDC. Levesque added that it needs to be confirmed in humans, but that it looks like TH1902 is first in class and best in class and that it will challenge the way cancer can be treated. Bold statement. For diagnostic tool, Marsolais said that they are working with a company developing histopathology tools. This is not the imaging possibilities I was talking about. They said nothing about using radioisotopes like Ga68 with TH19P01 for imaging or with Lu177 for treatment. In one slide they talk about the possibility of using the peptide with other cytotoxic agents, TKIs, etc... In this case TKIs are tyrosine kinase inhibitors, and etc is anything else you can thing of, but they don't talk about radioisotopes. In my view, not talking about the possibility of Ga68 PET scan is a weakness of their presentation today. It is not a dignosis tool, it is an imaging tool that would allow to predict much more precisely the suitability of treatment based on TH19P01, or the probability of success of success or the extent of success that can be expected. In my view, they will have to wake up the radioistopes option, and the first and easiest one to explore is Galium 68, because cytotoxicity is very low, close to none.
In the Q&A part Marsolais also reiterated what we already knew, the fact that in the IND toxicity studies, they were able to determine that rats could be given the equivalent of three times the MTD of free docetaxel. So it is a good indication of where they could end up with the MTD in humans. I also heard for the first time about patient derived xenograft models and Marsolais said it is the kind of models they plan to work on and that they will present stuff related to that next year at AACR. I join a link about patient derived xenograft, which seems to be grafting the actual tumor cells of a patient into a mouse to test what treatment could work. They confirm that they do biopsies on every patients that are enrolled in the trial at the beginning and test for sortilin expression. Marsolais also said they will do other biopsies during the trial, so as the treatment is going on, even biopsies on metastasis tumors. This is not stated in the protocol published on clinicaltrials.gov and is is a very important clarification. They won't go blind as the published protocol could lead to think.
Another thing, is the timeline for the second part of the phase I, the basket trial. I thought it would start somewhere during the fall, but now they talk about Q1 2022, but at the same time they say they have fast track designation and if efficacy is clear they will quickly meet with FDA to see the fastest way to get this drug approved. So uncertainty there at this point. In other words, mild efficacy will take more time, strong efficacy could speed up the process.
https://clinicaltrials.gov/ct2/show/NCT02247037