RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Meeting with management treating advanced cancers should be an advantage for TH1902. A lot of those cases will have developed resistance which TH1902 might be able to overcome and also the sortilin expression is higher in advanced cancers.
qwerty22 wrote: Green
SPCEO1 wrote: I will take a stab at this but you should probably hope one of scientific teamwill weigh in to get a decent answer.
See below in
red stockman75 wrote: Questions hopefully not too ignorent as I am much further down on the curve following all the details than the active posters here...
You said Christian mentioned some of the tolerability issues could be related to the condition of the patients not necessarily the drug.
Few questions come to mind related to this and MTD
1) would that mean in less severe cancer patients they could tolerate higher dose than the MTD?
I don't think that is what he meant. And, to be overly specific since they are related anyway, it is not the severity of the patient's cancer but the lingering impact of past treatments the patient had recieved. When you are eliglble for a phase 1a dose escalation trial, your body has already been beaten down pretty good by past attempts to cure your cancer. So, there is not much reserve left there and any new treatment likely triggers a fast negative response. The implication is if your body is not as damaged as these poor folks bodies already are, the negative impact of TH-1902 would be less.
While it's true these are difficult to treat patients, ever other cancer drug following this path has to treat this cohort of patients. So the head-to-head comparisons we will be doing and the bars that the regulators set for success/failure already take this into account. You can give them a little leeway at this early stage because the small patients numbers could get skewed by some particularly ill individuals but in the long run I think all this evens out onc you get into bigger patient numbers and the drug lives or dies on how effective it is in this group of patients.
2) would that require additional testing on less severe patients to allow for higher dose?
My guess is they already have taken this into account to some degree in landing on 300mg as the dose moving forward.
See answer 3
3) phase 1a is the worse condition patients. Does that move to less ill/severe cancer patients in phase 2b? If so then maybe they see less issues than those in 1b.
I am not familiar with the protocols on that but I suspect the patients beyond phase 1 are in somewhat better shape than those in phase 1.
I don't expect the description of the treatment group will change in 1b and it might not change all that much in 2a as well. Crudely speaking I think it is always going to be people who are towards the end of the road and the drug is always going to need to deal with patients who've had a lot thrown at them. Just like in question one the comparisons will be with other drugs that have gone thru this same process and got approval or are looking promising. They need to be competitive with those drugs in this patient population. There may be things they learn along the way that steer them towards better response rates but generally speaking I think they are committed to this late-stage patient cohort until the first approval.
SPCEO1 wrote: I hope patient number 2 has had that many cycles but I did not think that was what Christian was saying. I think he was suggesting (not saying, so this is my interpretation) it is possible based on what he has seen so far and that seemed to be that the cumulative toxicity of TH-1902 was nowhere near as bad as that of regualr docetaxel treatments. He said something like the regular docetaxel dosage is 80mg. 150% of that would be 120mgs and a patientmight well be killed by such a dosage afterjust 2 cycles. But because TH-1902 is different in that it is not targetting the bone marrow, it has nowhere near the cumulative toxicity that normal docetaxel has and thus 10 cycles were possible. Now, I am not a scientist, Christian speaks quickly and with a French accent and I am trying to take notes which slows down my ability to concentrate on everything he said. So, my take is almsot certain to have been off to some degree. But that is what I got in my notes and remember from the conversation.
It also fits with the pre-clincial work. But as JFM has pointed out, the phase 1a hit a toxic dose sooner than the pre-clincial work suggested it might. So, we await the details and we may have to wait until late June at the AACR conference to hear them. Overall, however, I was left with the impression they would be worth waiting for. Hopefully, that is an accurate impression and not a function of my own confirmation bias.
qwerty22 wrote: Yep, one of the things I meant to mention but missed out. That seems like a fairly wild claim at this point in time. Maybe patient #2 has reached 10 cycles if you include the early low doses, would seem possible. IDK.
Wino115 wrote:
I think the most intriguing fact mentioned is that the current read from what they know is that the plan of administration is to shoot for a massive 10 cycles. That would be 33 weeks under treatment which, if they can do it, would give them a nice lead in the progression free survival endpoint. Very intriguing that the CMO would say this as it's super positive in my book, obviously subject to the normal caveats.
SPCEO1 wrote: He did not qualify his statement - just said that what they are seeing in the trial matches up pretty closely with what they saw in their pre-clinical work. How you interpret that is up to you. I interpret it as a pretty confident statement about the trajectory of the trials but not more than that. We know if the trials continue to line up nicely with the pre-clinical work, than efficacy - actually significant efficacy - is going to be seen. It is still a big "if" but things are lining up nicely thus far.
palinc2000 wrote: I see you are now the messenger for the company...congratulations
However something in your message is very surprising
Indeed pre clinical studies and data were about safety (dosing etc,,) and of course efficacy in 6 or 7 cancer indications
So the CMO told you that the results in the clinical trial are closely tracking the pre clinical results...Did he qualify his statement at being solely for the safety part ?If he actually meant safety and efficacy that would be almost an impossible statement .....that would not be in a phone call with only 14% of the shareholders
SPCEO1 wrote: Zero shares since I report to you here about it. But the group on the call collectively controls about 14% of the shares.
palinc2000 wrote: This is fantastic news but how many shares do we need to hold to get access to such info?
SPCEO1 wrote: Along with three other large shareholders, I had a call yesterday afternoon with the CEO, CFO and CMO. I don't have a lot of time right now to summarize it well but it was an encouraging call. On cancer the CMO said the results are tracking close to what they expected from the preclinical work. I will post more later but the main takeaway is that cancer seems to be on a good path.