Mohit Bansal: Just wanted to get some color on how do you — talked about sweat chloride improvement with the vanzacaftor trial. Is there a correlation between the amount of sweat chloride you reduced versus the SCD [ph] improvement. If I’m not mistaken, the improved — the sweat chloride improvement was about 30% more than the dry cast combo, this combo. So just trying to understand how should we think about the bar for SEB that this new combined?
Reshma Kewalramani: Mohit, I think you’re talking about the vanzacaftor triple, that’s our next-in-class regimen for CF. This is the program that’s in Phase III and we expect to complete both studies in the 12-plus-year-old age group and the 6 plus year age group this year with results from that pivotal program early next year. With regard to your question on sweat chloride and ppFEV1, yes. There is a very strong association between improvements in sweat chloride and improvements in lung function. And you can see that across all of our previous CFTR modulators, all the way from KALYDECO through ORKAMBI SIM and TRIKAFTA. So that relationship is strong. In terms of what you should expect from the vanzacaftor triple. Or let me put it another way, the reason we have such high enthusiasm for the vanzacaftor triple, in the preclinical experiments, including the very important HBE assays which have been not only qualitatively predictive but quantitatively so, the vanzacaftor triple, I know this is hard to believe in a tall order but the vanzacaftor triple preclinically is even better than TRIKAFTA in our HPE cells.
And when we look across the Phase II studies that have been done, the vanzacaftor triple have better sweat chloride than even TRIKAFTA. It’s hard to call — make a call on ppFEV1 because in the Phase II studies, the sample sizes are obviously smaller and ppFEV1 is a more variable endpoint. So I think the right measure to look at is indeed sweat chloride. And from all of the data we’ve collected, vanza is even better than TRIKAFTA on that measurement of sweat chloride.
Operator: The next question is from Michael Yee with Jefferies.
Michael Yee: You announced that the chronic pain neuropenic pain study, Phase II was complete enrollment. So that’s super exciting and the data, I guess is end of ’23, early ’24. Can you talk a little bit about, I guess, on one side, you feel confident because of the biology and the acute data was also quite strong, there’s also some early chronic data as well as the last gen. But also, I guess, historically, chronic pain studies can be challenging with placebos, even with vicoden and opioids, you can get mixed results. So I just wanted to ask about your confidence around this probability success versus the acute study and how we should take this study into consideration from an expectation standpoint, give it just a Phase II?
Reshma Kewalramani: Sure. My confidence level in the VX-548 program is equal for the acute pain studies in that Phase III program as it is for the diabetic peripheral neuropathy Phase II program. And you’re right, that confidence comes from the pharmacologic validation of the target which we ourselves conducted with our predecessor molecule, VX-150 and also the genetic validation of the 1 8 target. With regard to double-click on what you could expect from both acute and the neuropathic pain studies, the acute pain program is 2 randomized clinical trials in the same bunionectomy, abdominoplasty. Those are 2 of the RCTs. And the third is a single-arm safety and efficacy study to allow a broad, moderate-to-severe acute pain label in the various settings that Stuart described in terms of use.
