RE:RE:RE:RE:RE:Canaccord ups Price Target to $7 These are my numbers for doses in the dose escalation phase in terms of docetaxel equivalent amounts, it's my math so it might be wrong.
1) 12.5
2) 25
3) 50
4) 85
5) 130
6) 180
7) 240
The MTD of docetaxel is usually given as 115 and the drug is usually administered at 100. That means the 1st four doses of Th-1902 are below the MTD of docetaxel and the top dose is only double the MTD of docetaxel.
From memory some things that have been said or shown for th-1902.
1) The drug accumulates at 7x higher amounts in cancer cells compared to docetaxel (I think Paul said that). If that's true and follows thru in humans then you might see efficacy in the 1st or 2nd doses.
2) The drug has performed better at 4x lower doses than docetaxel in preclinical models. If that's holds then you might see some efficacy at the 2nd or 3rd dose.
3) The drug is 3 x less toxic than docetaxel (I think Paul said that). If that's true then we may not actually reach the MTD in that range although the 7th dose comes very close.
So the best case scenario is we reach a recognizable efficacy signal at 2nd dose and toxicity at 7th (or never). Anybody believe their dreams come true?
But if there's non-cancer cell targeting the whole safety profile changes or if the drug doesn't perform the same in real-world tumours compared to man-made model tumour then the efficacy profile changes. Both those features are independent of each other and would influence where things land or might even sink the boat.
I guess the big question is how reliable are the preclinical models?
qwerty22 wrote:
I don't think you can assume that because it's not going into healthy cells it must therefore be going into cancer cells, it's very possible not enough goes into either cells and it mostly ends up in the toilet.
There is also no logic to what SPCEO is saying either, you can't assume that if we avoid toxicity therefore we get efficacy.
The first bullet we dodge is toxicity, the 2nd is no efficacy signal, there is no great link between both in my view. The features of the drug and its interactions in the body that allow it to pass the safety test are not the same features that will give it efficacy or at best they are tangentially linked.
jfm1330 wrote: Since they cannot visualize if the PDC is really going mainly to cancer cells, like it is the case for Lutathera, the only way to have an indirect proof of that early in the process is through safety data. The toxicity of docetaxel is well known, which means they know at what dose you start to see toxicity signs, and it goes worst as dose is increased. So when they will reach these doses in the dose escalation phase of the trial, if there is no sign of toxicity, like neutropenia, or much weaker signs of toxicity, it will mean that docetaxel is going mainly into cancer cells and not much into healthy cells. So this will be an early sign that at least the drug is mainly going where it should. So odds of efficacy, if it's the case, should be higher. That being said, you would still need the linker to be cleaved inside the cancer cell to allow free docetaxel to be active.
SPCEO1 wrote: Assuming no further delays, which may be assuming too much based on past experience, we have beentold to expect safety data from the cancer pahse I in late summer and efficacy data by the end of 2021. To me, however, if TH 1902 is shown to be safe, I think the liklihood of it being efficacious as well must be high since we already know the cytotoxic works. I am sure medically it is much more complicated than my simplistic view, but if it is safe, we probably can safely assume there will be some tumor response.
Wino115 wrote: I guess the upshot to that is if there is any safety and efficacy data on cancer he will have to increase it a fair amount. Then, when the Phase 3 starts he'll at least have to build a model and assign some kind of success probability to it.
The only issue here is that his firm is for sale and he/they may or may not be around or have different ownership that shuffles coverage and analysts around. I'm sort of the view now that it's been on the block so long and the markets have rallied so that if anyone were interested we'd have seen somethiing. From the newspapers it appears there's interest in their wealth management area so maybe they split in two eventually or someone buys that half.
Anyway, glad to know he's woken up from his Cheeto's coma...
SPCEO1 wrote: Ed Nash has finally published a report and he upped the price target on THTX to $7 from $6. He is doing so primarily based on a better sales outlook for the legacy drugs. So, still not much credit for NASH or cancer although both are mentioned favorably.