RE:Therapeutic windowIf they did not see something they could alter to hit the sweet spot of manageable toxicity and efficacy I imagine the trial would have come to a permanent stop. So, they must have something they are holding onto for hope. That suggests some efficacy has been seen which might be repeatable with a less toxic outcome or vice versa. But it likely needs to be something where the chance of success is pretty high for THTX to be able to justify spending additonal funds on it. Since that seems unlikely, I am assuming the TH-1902 trial never restarts and hope to be proven wrong.
Also, this is a long way from where expectations were for a very long time of a safe and effective TH-1902. Is it typical for the human results to vary so significantly from the pre-clinical? I really thought there was a very good chance THTX would get through phase 1a and 1b with little difficulty and decent results, albeit not as good as the pre-clinical results. That would have allowed them to raise money and keep things going on an even keel for a considerable period of time. We were supposed to see some phase 1a results published in 1Q23 - I am guessing we will not see those now or, if we do, we may not like what we read. There was a reason that portion of the trial took so long and we will likely hear what those reasons were if they do publish that info.
qwerty22 wrote: We are in the dark but the pessimistic take atm is effectively the therapeutic window is non-existent based on the present dosing schedule. 1a says go too high a dose and you have unacceptable toxicity. Go with the 1b working dose and you have unconvincing efficacy. You have some individual efficacy signals in 1a, it would be nice to know they have some in 1b as well, but at the population level it's not enough.
They should know something about drug exposure so they should be able to come up with a "better" dose but it's less certain they know exactly what the problem is so to me it's uncertain whether the "better" dose will fix the problem. Based on the present drug design they could be looking for a pretty narrow sweet spot of acceptable toxicity and efficacy, it also may not even exist.
I can understand not wanting to give up on Sortilin as a cancer target but a redesign might be necessary. I can imagine scenarios where either the payload or the peptide or both could require a redesign. This takes you back to step one and is commercially unattractive and investment-wise uninteresting.
Hunting for a "sweet spot" might be risky/uncertain/futile but if you can get a relatively quick answer and you can afford to splash a few more millions it is maybe commercially more attractive.
They are in a pickle.