RE:RE:RE:RE:RE:Dose escalation ... assuming it penetrates the tumours efficiently and get's to the receptors.
... and assuming the heterogeneity of the tumours doesn't have an effect of "masking" an efficacy signal.
Saying "only" is a very dangerous thing in science.
jfm1330 wrote: The only way they see very low free docetaxel and the PDC is not working as planned is if the linker would not be cleaved at all inside the cancer cells. If TH1902 stays in the bloodstream long enough because it is not internalized by sortilin, the linker would be cleaved and free docetaxel would be released in the bloodstream and they would see higher concentrations of it. The curve would be flater, with lower peak concentration, but still, it would be a much higher concentration than what they saw in the animal model. A concentration high enough that they would see toxicity coming much sooner than expected. If they look so optimistic at this point, my guess is because the free docetaxel they see is in line with a PDC that is working as planned. No toxicity at 300 mg/m2 would not be a defenitive proof of that, but if they clear the bar at 420 mg/m2, which would be close to two times the maximum tolerable dose of docetaxel injected alone, then I think it would be conclusive that the PDC is internalized by cells expressing sortilin.
SPCEO1 wrote: Unfortunately, we are all humans here, no robots. We are are all stuck with some degree of confirmation bias. But since we seem to have different views here, we can at least challenge it among one another when we think we are seeing it. And we see it all the time.
qwerty22 wrote: It's tempting to think the two things are linked. Cantor want to know they aren't getting on a train that's about to come off the rails. Thtx need to get the market moving.
BUT WE MUST AVOID CONFIRMATION BIAS! :)
jfm1330 wrote: Based on my estimation, we are now at least two weeks after the 300.6 mg/m2 dose and no news of toxicity. Instead we have the ATM news with a credible US broker. To me the likely plan is to raise money when the stock price will sharply rise on good news. Remember the rise after the approval of Trogarzo. We saw a lot of volume over a months and a half. If we see a similar raise this time, between 10$ and 15$ per share, it will be relatively easy to sell the necessary number of shares to raise the full 50 M$ without keeping the SP down.
For all the stuff we see here over and over about communication, promotion and all that, in the end it's the quality of the science that will win the day for us shareholders. All the rest is just noise. Promotion without substance leads nowhere, real clear good results will do the promotion job by themselves. This kind of ATM deal only makes sense if you expect a sharp rise of the SP on large volume and this will only come in the foreseeable future with a great news in oncology.
jfm1330 wrote: I went back to the KOL presentation to determine at what dose Thera likely is right now in the dose escalation trial. Marsolais said it take three to four weeks for every cycle. It was annouced on March 23 that they injected the first patient of the trial at 30 mg/m2. So taking that date as the starting point it gives this assuming a full four weeks for every cycle, which is likely not the case, especially in the first two or three cycles. Anyways, it gives this
March 23: 30 mg/m2
April 20: 60 mg/m2
May 18: 120 mg/m2
June 15: 200.4 (on June 21, Marsolais said they were close to the MTD of docetaxel of 230 mg/m2. So this is in line with what he said then)
July 13: 300.6 mg/m2
So it gives July 13 for the first dose well above the MTD of free docetaxel. Again, Marsolais said three to four weeks per cycle, so more than three weeks, but in some cases, probably in the first cycles, with one patient, less than four weeks. So this dose of 300 mg/m2 has been likely given somewhere between July 5 and July 15. Likely in the middle of that interval. So it is easy to understand why Marsolais willing to say in the last CC that they will surely have a MTD of TH1902 that is higher than the MTD of free docetaxel. Also, he probably already had the dosing of free docetaxel over time in the blood after the injection of the 300 mg/m2 dose. So he knew the level of free docetaxel this dose was generating. If the number was as low as expected, it confirmed to him that toxicity at that dose was very unlikely.
The next step will be 420 mg/m2 on August 10. This will be close to two times the MTD of free docetaxel.
Then, if they get there, it would be 558.6 mg/m2 on September 7, and 742 mg/m2 on October 5. This would be a bit higherthan three times the MTD of free docetaxel, which is what they saw on rats in the preclinical.
So we are sure to have a significantly higher MTD of docetaxel with TH1902. At this stage the only question to answer is how much higher will it be. The higher it will be, obviously, the better it will bode for efficacy. This helps understanding why they are so confident with TH1902 anf the SORT1 approach in general. Why they hire people to coordonate preclinical and clinical work. It also allows to understand why they were willing to write in their last press release, and say through the CEO in their last CC that they believe that They have developed a targeted peptide-drug conjugate that may potentially transform the way cancer is treated. These are their words, not mine, and this is a very bold statement coming from them. I can't figure how they can be more positive than that without releassing real good results. After such a statement, coming out in a few months with negative results would be an absolute surprise. But again with this company at this time, it is a matter of credibility and they obviously don't have much with the market. So this statement went by like it was never made. Even here, I have been the only one underlining it. So we will have to wait for the real results. It will either be a shocker for many, or a big disapointment for me.