Michael Cooreman: Sure. Yes. I think to start with LEGEND we actually have based the sample size calculation on the power, on the data that we have from NATiV2 on the effect on HbA1c. I don’t have in my head now but those numbers we have, and also on the additional benefit that you expect when you combine pioglitazone with one of the SGLT2 inhibitors. And as I mentioned there are four large randomized trials that give actually a consistent picture that you have an additional benefit on the decrease of HbA1c after half year of treatment or longer. But most of these studies was half a year. And that provides the basis to define an effect size as we should see, and a power calculation to have on a p-value that is adequate, that’s what it’s based on.
Now, it is a proof of concept studies. So I like to point out that this is really because we €“ this is the way we do it, but the main importance of the study is really to show that there is an additional benefit of the combination on metabolic markers, for those patients who may need it, and also on weight for those patients who may find it important. I can only repeat that to weight gain with PPAR agonist distinct from weight gain that results from poor lifestyle. But that may still be an issue for patients who are obese not all patients with NASH or NASH and type 2 diabetes or obese. So it’ll actually not be an issue for all patients, for some maybe, and this is what it’s based on. So we really see the value of this study in providing that set of data on the additional benefits that the combination we have in certain patients for whom this may be important.
And it’s in line also with how metabolic treatments, sorry, metabolic diseases are treated such as type 2 diabetes. And physician will start with treatment and then see how the patient enrolls and may add another treatment if necessary in certain patients. So with regard to the biopsy it was always our intention to start with three biopsy €“ with three expert pathologists. And we have started with two and have as soon as the third one was on-board, contractually made the tiebreaker process put it in place that does not really affect the patients that we enroll as eligible. In fact, we have looked at patients who are screen failed based on the initial two biopsies and see which patients would be eligible if the €“ or when the third one comes in as a tiebreaker.
And some of these patients would then be eligible again, but or would become eligible. But the key point is that the either the tiebreaker system gives a degree of stability, I think in the histology scoring. That’s an important aspect, of course, but for the evaluation of efficacy at the end of the 72-week treatment period, all histology will be reread. So the histology at inclusion and the histology at the end of treatment will be evaluated again by the three pathologists according to this pattern. So for the entire study, if you look at the evaluation of efficacy, the reading will be consistent.
Operator: We have no further questions at this time. I hand back our conference to Mr. Cren for closing remarks. Thank you.
Frédéric Cren: Yes. Well, thank you very much for attending. We have in front of us very exciting 2023, NASH the very exciting space. It was not the case last year and we see now a much more renewed interest. There’re going to be quite a lot of events this year, especially with the FDA, the Intercept and the Madrigal submission. And concerning the lanifibranor will remain confident. We have in our €“ and the drive that can make it to the finish line. And this year, operationally we know we have to deliver on NATiV3. And as I mentioned it seemed that we’re on the right track. And then we’ll also be looking forward with optimism, let’s say the crucial optimism to the data that will be generated by Professor Cusi in the type 2 diabetes study, and also of course in the LEGEND study, and that will keep us busy. And as usual, thank you very much for attending, and I look forward to seeing you €“ all of you in the future meetings.
Operator: Ladies and gentlemen, this concludes today’s conference call. Thank you for participating. You may now disconnect your lines. Thank you.
