At least one ENPP1 blocker appears to be in clinical trials already: https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&rank=2 https://clinicaltrials.gov

At least one ENPP1 blocker appears to be in clinical trials already: https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&rank=2 https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&ra.... It lists "advanced cancers" as being eligible. I'm most interested in head and neck cancers, and pembrolizumab (Keytruda) is only effective in 20 - 30% of patients; see e.g. https://ascopubs.org/doi/full/10.1200/JCO.21.02198 https://ascopubs.org/doi/full/10.1200/JCO.21.02198: "In the phase Ib KEYNOTE-012 study of pembrolizumab monotherapy in R/M HNSCC (N = 192), objective response rate (ORR) was higher in patients with PD-L1 CPS ≥ 1 than CPS < 1 (21% v 6%; one-sided P = .023)." A lot of oncologists I've talked to also think PD-L1 expression is overrated as a marker of pembro effectiveness; obviously there's something going on, with higher PD-L1 expression being net better in terms of pembro utility overall, but the data are noisy and lots of exceptions abound. I'm also not sure how reliable PD-L1 expression tests are. My tumor was tested once by a well-known-in-the-field company called CARIS, and it showed a 20% Combined Positive Score (CPS). Another test done by the Mayo Clinic showed a 5% score. Who's right? Who knows. No one I've talked to. The attitude seems to be that no one is convinced the PD-L1 tests are highly accurate, and that once the CPS is above 1%, pembro's effectiveness is a crapshoot anyway. I got five doses of pembro and failed it, utterly.