RE:RE:RE:Letter The analysis of the TH1902 program is quite easy to make, unless they have data showing that it could work in some sub group in a cancer type, or introducing biopsy confirmation of sortilin high overexpression in a new protocol, it should be dropped. And even with the addition of biopsies, I am not sure it would be worth continuing it.
As I wrote previously here, there is no targeted PDC approved in which the warhead is a cytotoxic drug. The one that went the furthest on that path was Aeterna Zentaris' Zoptrex, in which the warhead was doxorubicin, and it failed, despite going up to a pretty large phase III. One of the possible explaination I found for Zoptrex failure in humans was that the linker was not stable enough in the microenvironment of the tumors, outside cancer cells. Zoptex had glorious results in animal models like TH1902. The key is how it behaves in real patients with complex tumors, not a xenograft of a single cancer cell line.
Remember, one of the main difference between sucessful PDCs using radionuclides like Lutathera and candidates using chemo drugs like TH1902 or Zoptrex, is the fact that the former has a stable linker, not a cleavable one. This eliminates a big variable from the equation. No need to have a linker stable enough in the bloodstream, but not stable inside the cells. PDCs with so called selective linker will leak drug in the bloodstream. It's unavoidable, while radionuclides PDCs with a very stable linker won't leak the radionuclide at all. So the toxicity is much easier to control that way. On top of it, imaging capacity allows to exactly know where the PDC is going in the human body, in tumors, but also in healthy organs.
All that to say that I reiterate what I already wrote here after the news on TH1902. If their data is showing that some of TH1902 is going into human cells expressing sortilin, which is the critical part of the proof of concept if you want togo with a new PDC, then they should go back to preclinical, ideally with the radionuclide chemistry. It already exists and it's patent free. So do the preclinical work on that and try to find a partner to push it forward. It would eliminate the Trodelvy blockbuster scenario, but it would still have a lot of value, even with a partner involved.