RE:Dose escalationIn the last KOL presentation in June, Marsolais said that they expect to reach a toxic dose at the end of the summer or begining of the fall (time: 41:45). So based on my calculations here, based on Thera's plan for dose escalation, it means that they expect a MTD of two to three times the MTD of docetaxel injected alone, so between 500 and 800 mg/m2 of TH1902. After MTD is reached, he said that they will need to two more cycles to confirm potential efficacy. So we know their expectations, it is to reach MTD somewhere in October, then follow that with two three weeks cycles with the right dose. So the should have final results somewhere in December, but again, Levesque opened the door for it to be a little bit longer, so maybe one dose increase higher than they expected. So all that is good news.
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.