Reactie BioBoyScout
First off, the patients in this study are not screened for the VHL mutation, so therefore, only around 80% of the patients should, theoretically, respond appropriately to this drug. I don't think there's an issue of targeting alpha-v-beta-3 receptors on the tumor, and that's not something you test for. Alpha-v-beta-3 receptors could also be found on various other tissues in the body, and the drug would also get delivered to those tissues; if the bioinformatics is done correctly, then the target sequence in the drug will not do anything in those other tissues because there's nothing there to knock down. The bigger question is, does the patient have the VHL mutation, and are they seeing enough knockdown of the HIF2a gene (and is it having an impact by allowing the VHL tumor suppressor protein to be activated). So the goal is to knock down HIF2a so that it no longer suppresses VHL, as we want VHL activation (a darn good reason why it takes time for this drug to work and why it's not going to be working for everyone, as proven by the Peleton drug).
We also know that these patients have had numerous other treatments for their cancer. It is known that prior treatments can have an impact on the ability to activate VHL, so this can affect the effectiveness of the drug. We don't know if the HIF2a expression is the primary reason for the cancer, which is why it would make sense to combo this drug.
We do know from this study that there is target engagement. It appears that the alpha-v-beta-3 targeting ligand is getting the target sequence to the tumor like it's supposed to, and that they're able knock down the HIF2a gene. I believe that the ability to partner this drug depends on how effectively (and safely) they're able to knock down the HIF2a gene and reactivate VHL. It definitely looks promising, and would be a great weapon for doctors to have in fighting cancers because of HIF2a (particularly if anemia is a concern, and it usually is).
So will this drug get licensed or partnered? I think it should, and I think it would give the Peleton drug, Welireg (Belzutifan), a run for its money. Come on Chris, show me the partnership.