Mohit Bansal: Great. Thank you very much for taking my question and congrats on all the progress. One question again, staying on DPN and study. So could you remind us how prevalent is the opioid use in this setting because from our reading it seems like it is more a third line agent. And is the thought to replace Lyrica in that setting or is it more like to replace opioid in that setting? I mean, how do you think about the profile of the drugs? Thank you.
Reshma Kewalramani: Sure. I’ll have Stuart talk about what is being used in DPN today.
Stuart Arbuckle: Yeah, Mohit. There is a lot of polypharmacy going on in DPN right now, largely because the efficacy of the various classes of pain medicines which are available today is pretty variable. So you do see patients who are on nonsteroidals, you see a lot of people who are on the gabapentinoids which have been studied and approved there and you also do see parents — patients on opioids as well. So it really is a disease characterized by sort of polypharmacy, largely due to either variable efficacy and/or the adverse events of the currently available therapies. That’s why we’re so excited about the prospect of 548 being able to establish a new standard of care for these patients.
Mohit Bansal: Excellent. Thank you.
Operator: The next question will come from Jessica Fye with JP Morgan. Please go ahead.
Jessica Fye: Hey guys, good afternoon. Thanks for taking my questions. The press release makes mention of Vertex’s portfolio approach to R&D and additional NaV1.8 and NaV1.7 inhibitors you’re working on. How far along in development is the next most advanced 1.8 inhibitor behind the VX-548? And do you have any dual 1.8 and 1.7 inhibitors?
Reshma Kewalramani: Hey, welcome back, Jess. Really terrific question. The portfolio strategy, as you’ve seen it play out in CF, is authentically and reproducibly extended across our R&D pipeline. So as it pertains to pain, the next NaV1.8 inhibitors are already in the clinic in Phase 1 trials. And we have more after that making their way through the research part of our organization. In terms of NaV1.7, they are in the research stage and making very good progress. And we see the NaV1.7s as potentially for use as a single agent. And we also see the real opportunity for combining NaV1.7 and NaV1.8. And just for all of the others who are following along, the reason I say that and the reason I think it’s an excellent question is that, the way that the action potential works in the periphery in transducing the pain signal is that there is a stimulation of the action potential and then the propagation and NaV1.7 works on that stimulation of the action potential and NaV1.8 works on that propagation.
So we see a lot of opportunity in the combination, but we also see opportunity of NaV1.7 in and of itself.
Jessica Fye: Thank you.
Operator: The next question will come from David Risinger with Leerink Partners. Please go ahead.
David Risinger: Yes, thanks very much. I have two questions, please. First, if VX-548 succeeds in Phase 2 in DPN in coming months, how do you plan to conduct Phase 3? Do you plan to go it alone? And could you complete Phase 3 in 2025 or likely not until 2026? And then regarding VX-548 acute pain Phase 3 studies, how should we expect rescue medicine use to potentially benefit patients in the placebo arms, and how will rescue medicine use be disclosed? Thanks very much.
Reshma Kewalramani: Okay. Hey, David. Let me start the answer to both of these questions, but the PNP question has a component of can we go at it alone? And so I want to make sure that Stuart touches on it. Let me cut to the punch line. For acute pain and for neuroplastic pain, both in terms of diabetic neuropathy and in terms of LSR, this lumbosacral radiculopathy, we are going to do the development by ourselves and we are going to commercialize by ourselves. Both of these, acute pain and neuropathic pain are absolutely Vertexian diseases if I can call it that in terms of commercialization. I’ll ask Stuart to comment a little bit more on commercializing neuropathic pain and I’ll come back to tell you about acute pain rescue meds, etc.
