RE:RE:RE:RE:RE:TH-1902 pause is no reason to blame management Problems with the spacerbar on my computer. Here is a corrected version.
Many here thought that management was not promotional enough. We now see that they were too promotional. That being said, I don't think they were misleading investors. The key to cancer they were bragging about is not TH1902, it's TH19P01, the peptide that is the ligand to sortilin in animal models.
I always had my reservations about docetaxel, and about the selective cleavage of the linker within cells expressing sortilin. To this date, there is no PDC carrying chemo molecules that is approved. As I wrote here before, Aeterna Zentaris had a major clinical failure with a PDC (AEZS-108 or Zoptrex), a PDC carrying doxorubicin as a cytotoxic agent. They went to phase III before declaring failure. The good news for Thera is that they were just in the beginning of phase Ib.
At this point the danger is not for them to drop TH1902, it would likely be to persevere in a mistake and continue to spend money on it. That being said, it does not mean that TH19P01, the "key" to cancer cells is now worthless. If it's really the key to cancer cells expressing sortilin, there is another way to get value out of that asset.
You will say that I have a fixed idea, yes, it's true. But if you look at the landscape of PDCs, or PDC like drug (targeted drugs on a carrier that are not ADCs), you will see that the only two approved drugs are Lutathera and Pluvicto (Lu177-Dotatate and Lu177-PSMA) both are using the same cytotoxic agent, Lu177, and the same linker, DOTA. In the case of Pluvicto, peptide is replaced by a small molecule called a peptidomimetic. So it is not per se a peptide but it acts like a peptide.
So the key is to have the "key", the peptide or the peptidomimetic. Thera is claiming that they have the key, the peptide, TH19P01. It would be very easy to put the DOTA linker on TH19P01 and a radioisotope. They could do Lu177 and Ga68 on animal models, then if they are behaving similarly and appropriately, they could start a phase I "proof of concept" with Ga68, which has very low toxicity. Just to show the peptide goes into tumors and see where else it goes. If everything is OK, then you start a phase I with Lu177 on patients screened for sortilin overexpression with Ga68.
This chemistry and its toxicity is now well known. To do animal studies and phase I with Ga68 would not cost a lot. And by doing so, they would finally understand how their peptide is behaving in real patients with real tumors. Yes it would be a relatively big step back, but at least there would be no potential problems of selective cleavage of the linker. With radionuclides the linker is stable and you don't want cleavage. Also, Lu177 is a proven cytotoxic agent working not only on the cells in which it is internalized, but on many layers of cells surrounding it. Lu177 also bypasses any resistance to chemotherapy.
So my point is that they may still have value in their hands with TH19P01 and switching to DOTA-Lu177 and DOTA-Ga68 would be a wise move. Known chemotoxic effect and bypassing resistance to chemo, and precise screening of patients really suited for this treatment, all that with a chemistry proven in two approved drugs with many others in the pipeline and ADCs in clinical trials using it. But to do that it would require humility and vision.
jfm1330 wrote: Many here thought that management was not promotional enough. We now see that they were too promotional. That being said, I don't think they were misleading investors. The key tocancer they were bragging about is not TH1902, it's TH19P01, the peptide that is the ligang to sortilin in animal models.
I always had my reservations about docetaxel, and about the selective cleavage of the linker within cells expressing sortilin. To this date, there is no PDC carrying chemo molecules that is approved. As I wrote here before, Aeterna Zentaris had a major clinical failure with a PDC (AEZS-108 or Zoptrex), a PDC carrying doxorubicin as a cytotoxic agent. They went to phase III before declaring failure. The good news for Thera is that they were just in the beginning of phase Ib.
At this point the danger is not for them to drop TH1902, it would likely be to persevere in a mistake and continue to spend money on it. That being said, it does not mean that TH19P01, the "key" to cancer cells is now worthless. If it's really the key to cancer cells expressing sortilin, there is another way to get value out of that asset.
You will say that I have a fixed idea, yes, it's true. But if you look at the landscape of PDCs, or PDC like drug (targeted drugs that are not ADCs), you will see that the only two approved drugs are Lutathera and Pluvicto (Lu177-Dotatate and Lu177-PSMA) both are using the same cytotoxic agent Lu177, and the same linker DOTA. In the case of Pluvicto, peptide isreplaced by a small molecule called a peptidomimetic. So it is not per se a peptide but it acts like a peptide.
So the key is to have the "key", the peptide or the peptidomimetic. Thera is claiming that they have the key, the peptide TH19P01. It would be very easy to put the DOTA linker on TH19P01 and a radioisotope. They could do Lu177 and Ga68 on animal models, then if they are behaving similarly and appropriately, they could start a phase I "proof of concept" with Ga68, which has very low toxicity. Just to show the peptide goes into tumors and see where else it goes. If everything is OK, then you start a phase I with Lu177 on patientsscreened with Ga68.
This chemistry and it's toxicity is now well known. To do animal studies and phase I with Ga68 would not cost a lot. And by doing so,they will finally understand how their peptide is behaving in realpatients with real tumors. Yes it would be a relatively big back, but at least there would be no potentialproblems of selective cleavage of the linker. With radionuclide the linker is stable and you don't want cleavage. Also, Lu177 is a proven cytotoxic agent working not only on the cells that in which it is internalized, but on many layers of cells surrounding it. Lu177 also bypass any resistance to chemotherapy.
So my point is that they may still have value in their hands with TH19P01 and switching to DOTA-Lu177 and DOTA-Ga68 would be a wise move. Chemotoxic effect bypassing resistance, and precise screening of patients really suited for this treatment, all that with a chemistry proven in two approved drugs with many others in the pipeline and ADCs in clinical trials using it. But todothat it would require humility and vision.