Dr. Christian Larsen (CL): CD40, CD28. Boy, we spent a lot of time thinking about this. Our first work in our lab was in the early nineties. So we’ve been at this for a long time. I remember Jim Burdick asked me in Kyoto at the transplant meeting how long I thought it would take to get it to the clinic and in clinical practice. Being completely naive, I kind of thought about five or seven years. That was obviously incredibly wrong.
So I’ll loop back to belatacept in a minute. But the CD40 pathway, I think so much work has been done to de-risk them. I feel quite good about that, the thromboembolic I think is likely just taking off the table by good science and rigor. I do think that both sides of the pathway are potentially good targets. But I have to say that I think the evidence on targeting the ligand is pretty compelling. I think there was a lot of evidence of greater efficacy at different levels. Mandy Ford’s done some nice work suggesting alternative receptors for the CD40 ligand. Now we’re going to bring it to the test, there are a couple of candidates that are about to embark on trials or in trials.
So I would hope that there’s a path to safe approval and there are other targets trying to explore in rheumatoid arthritis. That helped us with the development of belatacept, to have a companion set of trials in autoimmunity, because we leveraged a lot of that. So I feel like we’re pretty well-positioned to explore how to use those drugs. I do think the combinations are good. I do think the CD28 pathway blockade targeting the receptor might have advantages. We’re poised to do a trial that’s taken awhile to get through the FDA and COVID hurdles.
But Lulizumab is one of the domain antibodies that blocks CD28 while they reject, it’s got a trial in it as well. That may spare TRegs. That may have advantages. It’s got to get through the path to approval to be useful. So I think because of the autoimmune work, I think it’s probably reasonable to include them in xeno experiments. I think that it’s quite likely that they will help.