jfm1330 wrote: I should add that the main problem now, at least for somebody able to understand the science, is that we have no hint at all about the proof of concept. 300 mg/m2 (1.3 times MTD of docetaxel alone) could be possible without a proof of concept. That mean a 300 mg/m2 could be tolerated by patients even if TH1902 is not internalized inside cancer cells by sortilin. A 300 mg/m2 could be tolerated just because the PDC is changing the pharmacokinetic profile of docetaxel, versus docetaxel injected as a free drug. Cmax of docetaxel with an inneffective TH1902 would be lower than the Cmax of docetaxel alone because the link with the peptide would make it a slow release system. So maybe that way, more docetaxel will end up in the liver without exerting its toxic effect on other cells.
Again, 300 mg/m2 is only 30% above the MTD of docetaxel alone. If there is a proof of concept, I agree that 300 mg/m2 could still be a valid therapeutic dose because of the concentrating effect of sortilin mediated internalization. But if there is no internalization, 300 mg/m2 of TH1902 could still be tolerated. That's why it is frustrating, because Thera has the pharmacokinetic data in human on TH1902 and did not disclose any of it to reassure investors. They have an idea of what is going on outside of efficacy and a real proof of concept, but are not sharing it.
When I talk about hints of proof of concept it's what I am talking about, pharmacokinetic data they have collected on patients, and also, possible correlation of that data with sortilin expression on individual patients. To me, 420 mg/m2, close to twice the MTD of docetaxel alone would have been a very strong hint about a proof of concept, because I don't think that such a high dose could be tolerated without the concept working, but 300 mg/m2 is just on the line to sow doubts. That's 30% more, sure, but not enough to be almost sure the concept works. So we will not have an advanced signal about proof of concept. We will have to wait for the results to be published, assuming they will publish enough of it. On the positive side, as SPCEO said, they would not plan phase Ib and even phase II without some data confirming a proof of concept. The problem for me, is that it's hard to trust them because they were wrong before about their own scientific assumptions. Remember also the search for a si RNA specialist. Why would you hire such a person without a proof of concept? If TH1902 does not work, putting siRNA on TH19P01 will not make the SORT1 concept work. So I guess we have to trust them not to be totally delusional.
jfm1330 wrote: On the commercial side, we need to recognize that Levesque got bad timing with Covid. It's hard to judge him properly on that because of this situation. Their NASH and oncology strategy was related. My guess is that they were very optimistic last June about phase Ia of TH1902. Expected good results published in october or November, and a rise in the SP following that. If the rise and the volume would have been important enough, they would have raised money using the MTD, ans then, with that money, they would have started the NASH trial with the goal of doing it by themselves up to the futility test. Also, good phase Ia results in November meant probaly interim phase Ib results in May or June 2022 and another rise of the SP. As we can see, nothing went as planned. That does not means TH1902 will fail, but it shows that all their plans are postponed by six months, and the SP is where it is because of that. Also because of the lack of information they gave about why the trial is so slow. I don't care much about the stock promotion thing. I don't believe in that, but I care about good execution of their plan, and on that they failed miserably. A positive outcome is still possible, but the execution was simply bad. Again, the toxic part of TH1902 (docetaxel) is well known. It should not have been that long. They knew the kind of toxicity to expect.
SPCEO1 wrote: Good post. That better explains the pickle they have got themselves in regarding the narrative they have created around the stock price. As you point out, they really cannot control very well what the FDA insists upon but they could have sold the whole thing to the market better by setting better expectations, especially since almost all drug trials go longer than initially expected. And I have to beleive that the first trial in humans is messier than most because they are flying blind when they start the trial.
Had they set expectations for the trial's timing better, focused more on the ability of TH-1902 to get more drug into tumors at even low doses and highlighted the potential advantages of more frequent dosing and longer dosing more, there may have been a somewhat better result. The focus seems to have been on getting a high MTD when I suspect that might not be as important as the other factors.
On NASH, they really walked straight into that PR mess voluntarily. But I imagine they were doing their best to put a brave face out there so as to make it seem like there was interest from multiple partners and create a more competitive situation for anyone that might have shown any interest. It was a weak effort that really did not stand much of a chance but I don't know how much I blame them for trying. Maybe we can get cancer results that are pretty good and NASH can just quietly fade away as it seems to be headed that direction already. If I were on the board, I am not sure how much enthusiasm I would have for doing a share offering or borrowing money to pursue NASH if cancer is something that should be the focus of the company.
On the legacy drugs, they have said Q1 will be a good quarter. I would just remind folks that Q1 last year was awful since they pushed sales into Q4 to be able to out out a press release talking about great sales just before the ONO. So, that was lying in my book. Again, standard lying by a small company raising money but they defintely distorted the truth there and we should remind ourselves when we see the Q1 numbers this year that the year-over-year growth is not really as good as it might first appear.
jfm1330 wrote: They were way off on timelines. Back last June they were talking about reaching MTD at the begining od the fall, so October. Then they revised it to begining of 2022. And now it's something like May 2022. You want to know why the SP is down. You cannot be so bad in your guidance on timelines. Add they changed their tune on NASH and stagnant commercial business. I am glad they changed their tune on NASH, but still, for the time being, they look very bad. They have nothing positive to put forward. They were way too optimistic and got a very bad phase Ia protocol with the FDA. They started at 1/7 of the MTD of docetaxel alone. This made no sense. And the all comers requirement made no sense either. Maybe that they had no choice but to accept those silly requirements from the FDA, but the result is a phase Ia that would have taken 14 months. This is crazy for a PDC using a well know cytotoxic drug (docetaxel).
PWIB123 wrote: Did they actually say all went smoothly? I don't recall hearing that, especially considering they released and acknowledged the neutropenia. I do remember them saying that the things they were seeing were consistent with preclinical.
canadapiet wrote: And they lied again!!!!!!!
They said the P1a all went smoothly, just like in the preclinicals............!
Look at where we are now..........
How long are the "people in the know" saying that there is "HOPE" ?????
Well, let us all "HOPE" that in the near future (?????again....) we can set a new high !!
Momo25 - (3/23/2022 9:54:30 AM)
RE:RE:RE:Stay focused on the facts
I bought THTX when Trogarzo was lunched. At that time Dubuc talked about a potential of at least 1 billion revenue. Then everything becomes inconsistent. Legacy drugs are covering for the costs only. NASH needs huge investment and big pharmas who are making money like ever are reluctant to put a penny in this program. Oncology was brought to the table since they bought katana and the results up to now are very tiny, if not insignificant.
I averaged down many times and i am still a bit below 6$ and I took a hit of 49k by selling half of my THTX portfolio. Many shhareholders are in the same situation where I am. This is our reality today. The rest is bla..bla