Welcome to the forum and thanks for your question. I think that antisense oligonucleotides (I’ll call them ASOs because it’s a long name to type) are based on good science and have a known mode of action. One of the major challenges have been to deliver them to the liver, but huge progress has been made in this area and it looks like this is pretty safe and efficient now. In pre-clinical models, ASOs have shown good effect on HBV DNA, HBsAg, and HBeAg.
The problem is it’s difficult to test the effect of ASOs on cccDNA because of the lack of proper models we have for a chronic HBV infection. The hope is that the reduction in HBsAg will restore some immune response, which will wake up and start clearing infected cells. Even if this is not achieved, ASOs may at least help achieve a functional cure (i.e. loss of HBsAg, which would mean you could stop taking antivirals).
My feeling is that there is promising data out there because a fair number of companies are investing in this strategy. Trials are currently ongoing, so we should find out soon whether they live up to these hopes!
@john.tavis might have some further things to say about this as a drug-discovery expert.