So

we have that in a single strategy is a single monoclonal antibody in Ionalumab.

But the combination of BAF targeting with Belimumab and B-cell depletion with Rituximab is an older concept.

So there's been the three major trials for lupus that have used that principle would be Calibrate and lupus nephritis, Lisbelieve.

And then in the UK, academic-initiated trial from UCH called Beat Lupus.

And they were powered for various endpoints.

But I think the signal that came through was, at least very clearly in Beat Lupus, was it did suppress the serological return of disease activity in DSDNA antibodies and did suppress, reduce serious flare.

Where was this improvement?

We all feel quite comfortable using rituximab to treat lupus, myositis, but actually the trial data is not really there to support that.

Yeah.

So, I mean, lupus in particular has faced a huge progression in kind of trial design and understanding of clinical endpoints and understanding how to optimise the kind of the delta of treatment arms versus placebo by kind of refining patient selection, enforcing steroid taper, minimizing background therapies or fluctuations in background therapies, particularly the glucocorticoids, and also just selecting the right patient cohort and verifying that you're treating active disease.

So that is something that's evolved hugely specifically in lupus.

And probably trial design was responsible for a lot of failed therapeutics over the years.

And probably we'd look back and say was contributory to the failures of the major rituximab clinical trials, Explorer and Luna.

So that has progressed a long, long way.

I think that has probably played a role in this as well, isn't it? And obviously things are changing, which we'll touch upon later.