And that also translated into a meaningful improvement in gut epithelial structure, the histology. So again, that’s the sort of downstream effect of reducing those autoreactive T cells. So as we said and you may have heard me say before, too, if we see a similar response in PBC, that would be quite impressive and potentially game-changing for the opportunity to help patients with PBC. But that’s where we see the data. The preclinical evidence is in PBC directly. The clinical evidence you hear about the 90% is from a celiac study done by — that’s published by another company.
Thomas McCourt: Mike, I’ve heard you say in the past that if we do see a dramatic reduction in T cells, it’s clearly a strong indicator of what you would expect to see as far as overall clinical response with regard to probably the impact and alk phos and bio cell or bile duct destruction.
Michael Shetzline: Yes, exactly. Because we really think we — based on the science, that this approach, CNP-104, and targeting the specific autoantigen of PBC, which is the PDC-E2 antigen, that, that is targeting the root cause of the pathology of PBC, which is the bile duct destruction. The T cells, the autoreactive T cells destroy the bile ducts. If we can decrease those T cells, then we should reduce or potentially eliminate the bile duct destruction of PBC patients. And again, the celiac data from proof of technology and proof-of-concept in patients actually showed that they’re decreased in autoreactive T cells. I mean celiac patients did improve gut epithelial histology.
Timothy Chiang: No, that’s helpful, Mike. Maybe just one follow-up then. The dosing in the celiac study, is that comparable in the dosing that you’re running in the PBC study? I mean is there anything comparable there?
Michael Shetzline: Yes. I think it’s a great question, and that’s why we’re studying 2 doses in the current PBC patients. So I think, clearly, there’s a reason to make the association. But I do think it’s also fair that different diseases may have a different pharmacodynamic response to doses. So we’re clearly open-minded in terms of as we do this study to be cognizant that we want to find the right dose in PBC patients. And that similarly, I’m sure what’s happening in the celiac space as well.
Operator: . Our next question will come from Boris Peaker with Cowen.
Boris Peaker: One question on CNP-104. You mentioned that the market is about 130 patients, if I heard you — 130,000 patients, if I heard you correctly. Can you break that down based on disease severity? And if there is any particular subgroup that 104 will be targeting?
Michael Shetzline: Yes. So I think it’s a good question. I think as with most liver diseases, this aspect of disease severity is important. And in fact, you probably know that with obeticholic acid, the label is indicated around aspects of liver disease severity in terms of not being advised in patients with cirrhosis or decompensated liver disease. So our program, because it’s obviously innovative and new in patient populations, is starting with more early liver disease patients with PBC. But the reality is the underlying mechanism should be broadly applicable to all patients with PBC. Because, again, we’re targeting the immunology behind the bile duct destruction. In using semisynthetic bile acids and other approaches, you could see a reason.
And as demonstrated with some of the semisynthetic bile acid labeling, that there might be a reason to have concern with some more severe liver disease patients. But if we’re — if the science plays out and we’re able to reduce those autoreactive T cells, that should be applicable to the broad population of patients. Now, again, we’re in proof-of-concept study. We got a long way to go getting data. But again, that’s why we like the program because it’s really grounded in the science of the real root cause of PBC.
Boris Peaker: Great. And my second question is, maybe you could comment on your thoughts on the impact of Inflation Reduction Act on LINZESS?
