Morning, everybody. Welcome to the Bank of America Healthcare Conference, our London version. I'm pleased to be kicking off the conference with our first presenting company, Vertex Pharmaceuticals, presenting for Vertex Pharmaceuticals. Sitting next to me is Senior Vice President of Investor Relations, Susie Lisa. Susie, good morning. Thanks for flying over from Boston. Thanks for having me. I think everybody in the room is quite familiar with Vertex as a company, so we don't need to do the two-minute elevator pitch. I think it would be good to get a sense of what catalysts are upcoming for the company in general, let's say for the next 12 to 18 months. Then we can go into a little bit more detail on some of those. Sounds good. Thanks again for having me. I think, as usual at Vertex, there is a lot going on. Maybe first and foremost, in terms of catalysts, I'd point to three ongoing commercial launches as we enter into this new phase of revenue and commercialization diversification. Engaging the launches for LifTrak, our fifth medicine in cystic fibrosis, of Casgevy for sickle cell disease and beta thalassemia, and for Jurnavix in acute pain. Beyond that, we have four ongoing phase 3 programs and a fifth to start soon. Just to run through those, and then I'll get to the catalysts within them. It's phase 3 programs for diabetic peripheral neuropathy in our pain franchise, for three in the kidney space, two that are ongoing, that's in immunoglobulin A nephropathy, that's POVI, as well as enoxaparin in APOL1-mediated kidney disease. The fifth to start soon will be in primary membranous nephropathy, and that's also with POVI. Finally is our Zomylacell program in type 1 diabetes. Upcoming catalysts there, beyond the launches, as I mentioned, will be before the end of this year. We said that we'll complete the interim analysis enrollment cohort for our phase 2-3 study of enoxaparin in AMKD. Once that cohort completes enrollment, then it is 48 weeks of follow-up for the interim analysis and hopefully an accelerated approval stemming from that. We'll complete that enrollment by the end of this year. As you move quickly into 2025, we also said by the end of this year, we'll complete enrollment in the full cohort for POVI in immunoglobulin A nephropathy. Those are two big enrollment milestones by the end of the year. Moving into 2026, we said to expect data for POVI in IgA nephropathy in the first half of 2026. We said that we'll complete enrollment in both of the DPN phase 3 studies in diabetic peripheral neuropathy in 2026. We'll also complete enrollment in the phase 1 to MAD/CAD portion of our myotonic dystrophy type 1 therapy, VX-607, and that you could see filings for both POVI and IgAN, as well as potentially regulatory filings for Zomylacell in type 1 diabetes. Quite a bit going on. Yeah, there is a lot to dig into there. Maybe let's start off with what the company has been traditionally known for, the CF franchise. As we think about the continued switchover, what do you think are going to be the key drivers that investors should be looking for in terms of growth potential for the franchise? For growth for the CF franchise overall? For the CF, yeah. I think that there are several key drivers. Perhaps the most macro of them all is just the survival benefits that our CFTR modulators bring. A baby born today who starts on our medicines is expected to live into their early 80s, right? That survival advantage is really driving overall market growth for us. We also continue to get approvals for our therapies into younger and younger patients. Trikafta is approved down to age two. Currently, LifTrak, our newest product, is approved down to age six. Kalydeco goes all the way down to one month old. It's actually granules that you can put in breast milk or formula. We will continue to do that so our patients can get on therapy earlier and earlier, driving into younger patients. There is some expansion into additional geographies. Lately, we've called out Brazil as one example of that. I would say longer term, or in the medium term, we have the ongoing approval with LifTrak. We have patients who are new patient populations there in terms of those who have rare mutations who are not eligible for Trikafta or other therapies. That's a few hundred patients in the ongoing launch in the U.S. It's more like a few thousand here in Europe, just given the geography of how the disease has developed. Bringing back patients who have discontinued other therapies with LifTrak and its benefits, different potentially patients who had side effect profiles that led them to discontinue, they are likely to try LifTrak again. It also offers the benefit of once daily dosing. Longer term, we see growth from the potential of VX-522, which is our inhaled mRNA therapy in development and co-development with Moderna. That addresses the final 5,000 patients or so who don't make any CFTR protein and would be another avenue of growth. OK, thanks for laying all that out. I maybe wanted to ask a little bit more about the switch rates because that's something that investors are thinking about from Trikafta to LifTrak. Can you talk about that, at least in the U.S. launch? Yeah, in the U.S. launch, we've been very pleased with the uptake so far. We have said there's really three populations to think about. There's that rare mutation or naive population that hasn't been on a CFTR modulator before because they weren't eligible. That was where we've seen the fastest uptake. That's a few hundred patients in the U.S. It's a bigger opportunity outside the U.S. and Europe where the launches are ongoing now. Second is sort of a steady cadence of discontinued patients as they come back for their quarterly visits with their physicians. They're aware of this new therapy and perhaps consider coming back on therapy. Perhaps it was a life event, why they discontinued, pregnancy or went to college, and once daily dosing is appealing to them. Or perhaps, as I mentioned, it was a side effect and this has a different profile. The majority of prescriptions, the biggest population, and thus the majority of prescriptions of LifTrak in the second quarter, though, are patients who switch from Trikafta to LifTrak. We've been pleased with that pace. In the U.S., there is additional liver monitoring requirement, right? That has taken sort of an extra step, a conversation between physicians and their patients to weigh the six months of the monthly monitoring that's required versus the lifetime of benefit of lower sweat chloride levels and once daily dosing. Lower sweat chloride, I think, particularly for CF patients now who realize their life expectancy, they want to do it in as healthy and as wholesome a manner as possible. Lowering sweat chloride, given that CF is such a systemic disease, will prevent and/or will stave off certainly acute things like pulmonary exacerbations, but also just preserve bodily function throughout the GI system, pancreas, reproductive system, et cetera. That trade-off, I think, is well worth it as the best CFTR modulator. Once daily dosing, because you have to take CFTR modulators with a fatty meal, that's actually quite a convenience benefit and can help in overall health management. Just to keep on that topic for one more question, how are doctors responding to that monitoring requirement? Do they need extra training? Is it more cumbersome for them in terms of having to bring patients in? How are they changing what they did before to adapt, at least for the first six months of treatment for the patients now? Good question. Sweat chloride is how the disease is diagnosed, right? If your levels are 60 or above, then you are officially diagnosed. A level of 30 is a carrier level. Parents of children with CF who are asymptomatic have sweat chloride levels around 30. It is not typically part of standard practice in terms of monitoring that. There has been educational work that we've had going on for years and has certainly elevated with the launch of LifTrak. Natural history, physicians understand this. Patients are beginning to understand it more and more. That has been a key driver. The incremental monitoring, and I should note, is only a requirement in the U.S. It is not part of the label in Europe, in the UK, or in Canada. It is six months of monthly monitoring. You don't have to go into your center. You can do it at a more convenient location if you live far away from your center. I think it really is a worthy trade-off for these lifetime of lower sweat chloride levels and once daily dosing. That is the conversation that's ongoing. OK, cool. Another question we get is about potential impact from MSN, if any, to LifTrak sales. Of course, it's still an evolving situation. We don't actually know the details. Overall, can you just talk about Vertex's pricing strategy worldwide and what you think in general impacts could be? Sure. It is very hard to comment on because there are so few details. We have very strong advocacy in D.C., a lot of planning going on in the event that this does come to pass. I think also exploring potential options and offsets that we could implement. I will say that, broadly speaking, because we're on our fifth medicine, it's not like we launched one drug 20 years ago and took annual price increases in the U.S., right? We have said that after the statutory discount in the U.S. for Medicaid patients of 23.1%, I think it is, that we are broadly in the same line, in the same range from an MSN-type basket of pricing. There certainly would be challenges, but I think we're relatively well-positioned versus some peers. I think foundationally, as a company, we target very serious diseases where we're trying to deliver this transformative type of effect. I think that often helps you in challenging reimbursement environments. That's where we'll continue to focus. OK. Related to that, tariffs in terms of manufacturing, just overall, how does supply chain work for production? Yeah, so again, I think relatively well-positioned versus peers. The majority of our manufacturing is done in the U.S. We're currently building a new facility with our partners, Lonza, in New Hampshire for our cell therapy product, primarily type 1 diabetes. To date, with what we know, there's been minimal impact. We'll see what happens with, I always forget if it's 232 or 233. We think we'll be relatively well-positioned and certainly have taken steps to minimize any impact in the near to medium term. Likely, it wouldn't be anything until 2027, even if it were to go into effect very shortly. OK, good to know. I did want to ask about providing any color on the dispute, I think, with Royalty Pharma as it relates to LifTrak royalties. Where does that stand? Should we be expecting to hear any updates on that? I can't say much, given confidentiality around it. I can confirm, as royalty announced on the day of our earnings, they informed us that they'd like to initiate a dispute over the royalty rate for LifTrak, which we believe is a 4% rate. That's how we are booking it. They believe that they maintain it something in the higher single digits. There is a set process that goes through. I believe they've stated they believe this should wrap up by year end of 2026. I wouldn't disagree with that. OK. As we look ahead, you've had now several generations of improvements upon previous products in the CF franchise. As you look ahead, as you think about CFTR modulators in general, can you talk about version 3.0? I think you've alluded to it. What is the science behind that? What is the ultimate goal? Is it to treat every patient or to be able to treat them as best as possible? If you could provide some color on that, because I know there's potentially some competition several years down the line. Yeah. Our longstanding goal has been to get all CF patients to carrier levels, so below that 30 threshold in terms of sweat chloride. With Trikafta, we're getting maybe 25%, 30% of patients there. In the pediatric study for LifTrak, we got a majority of patients there, just over 50%. Those kids could really be asymptomatic their entire lives. The goal for VX-828, which is the next-gen 3.0, as we somewhat confusingly call it, is to raise the bar on LifTrak and get even more patients to below that 30 threshold for carrier level while also maintaining once daily dosing. We have our proprietary human bronchial epithelial cell assays that have, over the years, become quite qualitatively and quantitatively predictive of success from benchtop to bedside. We're encouraged by what we've seen in 828 thus far and should be in patients with CF before the end of the year. Should we be able to see data over the next 12 to 18 months on that? We have not commented, just to stay tuned. Sure. OK. Maybe let's move on to the pain franchise. Can you talk about the progress that you've made so far in securing broad access coverage for Jurnavix? I want to call it Jurnavax all the time, Jurnavix. What additional work might be needed to gain full coverage? Yeah. I'll have to tether back to our earnings call. We'll provide updates on this. In early August, we were very pleased to recall this launch in the March time frame. By early August, we had already had what we call unrestricted access for 150 million lives in the U.S., 150 million lives total, 85 million of which were unrestricted. By unrestricted, we mean that there are no step edits, right, which really doesn't make any sense. You don't want to have to fail an opioid before you go to a non-opioid. There are, very importantly, no prior authorizations required. These are contracts we've negotiated for 85 million covered lives, where those are the two key points on our side of the table. We've been very pleased to get to that. The other 65 million to get to the total 150, I think there's been some confusion on the street. Those are parties with whom we just have yet to negotiate. They have proactively provided coverage, but there may still be restrictions to that coverage. Expect more of that 65 million to move into the 85 million bucket and the bucket overall to continue to grow. We said back in early August that we had two of the three major PBMs. Oh, and I forgot a catalyst because we said we'll get one of the third by the end of this year. At the time, we said, I think it was 16 state Medicaid plans and continue to make progress there. If you go back to prior to launch, there were a lot of folks who said you'll never get anyone to pay for a branded medicine when opioids are $0.20, $0.30 on the day. That's clearly not the case. There's a real unmet need in the market for additional options for pain management. Jurnavix is resonating there. I also wanted to ask about competition from acetaminophen and NSAIDs, for example. You said it perfectly. How are you thinking about strategy there? Some physicians have said that taking those for multiple days can, at least for post-op pain, for example, achieve the target. Those are also quite inexpensive. What is the real hook for Jurnavix when people are or when doctors are pitched the idea? I think one of the most attractive things about Jurnavix, in addition to its efficacy, is its clean, clean, clean profile, right? If you recall in one of our studies, I think it was the phase 3 for acute pain. The side effect profile is actually better than placebo in many ways because it's actually providing true pain relief. We also did not combine it, even though typically pain is multimodal, right, in our studies because we wanted a true measure of its treatment effect. I think you are seeing physicians increasingly get very comfortable with we're certainly marketing it on label. You're seeing some preoperative use, combination use. That's just the nature of the pain market, I think. No concerns there. Ultimately, I think that that's how the physicians practice in this market. Jurnavix fits very well within that. Is most of the use right now for, let's say, a patient who's being discharged from the hospital, they're given a script. Ideally, on their way home or close to it, they can pick up the script. Is that the ideal? That's right. As of Q2, and this is how the broader market has played out, it was about a 35/65 split, 35% sort of in-facility use if you think about it, and 65% at discharge, so filled in that retail setting. That's what the IQVIA scripts are tracking, is about that 65% of the market. We'll update that each quarter. In terms of access, for every pharmacy in the U.S., how quickly can the supply be delivered to the pharmacy so that the patient can have access to it? Yeah, because this is an acute market, that was a very key part of our launch strategy, was ensuring broad access at pharmacies nationwide. If it's not there, it's unlikely to get filled. We've had learnings along the way, but that's been a key focus. I think the availability is there. OK. In terms of average use per patient, how are they using it? Ultimately, we're just trying to figure out dollars per patient. Do you have a sense on it's still early in the launch on what those metrics could look like? The average script duration, if that's your specific question, has been about 14 days. That's consistent with the broader market. 80 million patients seek a therapy, a prescription medicine for pain. Over the years, that's been about the duration, and Jurnavix is fitting right within that. About 14 days on the discharge segment of it. I would just segue, if I may, from that into we've been really pleased with the breadth of the uptake, both in terms of different types of physicians who are prescribing it, ranging, obviously, anesthesiologists and pain specialists, docs, orthopods, general surgeons, plastic surgeons, OB-GYNs. Dentists are finding a good niche for that. With With a broad moderate to severe acute pain label, that qualifies for a lot. We've been really pleased with the breadth, and that's been our goal here in these first couple of months post-launch. What's the maximum amount of time a patient can be on it? The World Health Organization defines acute pain as 90 days. I don't think there's an upper limit per se. You can get a refill, but it has to be defined as acute pain to be on label. I would assume the average is 14 days, but you might see some that are significantly more, potentially. That's right. OK. Now, in terms of the movement into chronic pain, acute pain has always been in the realm of short-term use. Patients will cycle on, and when they don't need it anymore, they cycle off. In terms of the market potential, chronic pain has always been sort of the place to think about in terms of having a patient for long periods of time. How has your strategy changed from a year ago to now on how the company is seeing the pursuit of chronic pain? You did have an LSR study update last year, which is a little bit disappointing. On the two Q calls, it seemed like there was a little bit of a shift in tone about the process to getting, if not the broadest label possible, the piece of indications added on. Sort of a long question to ask, but love to hear your thoughts on that. Yeah, no, I appreciate how you asked it. We believe firmly in the unique mechanism of action for Jurnavix, which is inhibiting the pain signal before it can get to the central nervous system. In our view, and what we've seen in our predecessor molecules and with Jurnavix, is that it does work across all different types of pain, that being acute or chronic, even musculoskeletal, with our predecessor molecule VX-150. Therefore, our goal remains a broad peripheral neuropathic pain label, of which 10 million patients suffer from in the U.S. every year. Our hope had been originally to do one phase 3 study in diabetic peripheral neuropathy, which is about 2 million of the 10 million patients, and one study in lumbosacral radiculopathy, which is about 4 million of the 10 million patients, and go to the FDA with a proposal for a broad PMP label resulting from that study, and then an all-comers. That was very similar to what we did in acute pain with a bunionectomy and abdominoplasty and an all-comers. It was clear at our end of phase 2 meeting in July that the FDA is still thinking about peripheral neuropathic pain as different conditions. They are more focused on etiology at this point. If you think about it, sometimes the cause is a metabolic disease. Sometimes it's cancer, a toxin, et cetera. There are many different causes, and even locations, and sometimes even the sensation of the pain, more urgent versus sort of a generalized pain, constant pain, et cetera. It was, I think, a very productive conversation and meeting. What was clear from it is that our idea to do one phase 3 DPN and one phase 3 LSR study would not get us a broad PMP label at this point in time. The clearest feedback was to traditionally, as you have before, two studies in any indication, get that indication. Then one study could add on additional indication. Hence our communication that we would pivot and start a second DPN study as soon as possible. Our next steps are still to be determined because the agency in our discussions made it clear that our point was, oh, you can't expect us to do studies in every single subpopulation of this 10 million. They might be open to smaller subgroups. Not 60% of patients getting you the full pie, but perhaps something like mononeuropathies or polyneuropathies. That conversation we were encouraged to see was very well represented in the draft guidance that they issued last week or the week before. We are going through to essentially determine what's the next best, most efficient step to ultimately reach our goal of a broad PMP label. It may be after DPN. It may be another single indication. It may be a small grouping. It's still to be determined. We are encouraged by the ongoing dialogue we have with the agency. It's a little bit of a stay tuned. OK. On DPN, I think you have a study running out next year. We've said the first study actually began in December of 2024. The second study will begin imminently. All we have said to date is to expect enrollment to complete in both in 2026. We haven't given a timeline for data. They're 12-week studies with two weeks of follow-up. We're going to the same sites that are well-rehearsed in treating DPN patients and running these types of studies, managing placebo effect, et cetera. It'll really be sort of which one goes in. We'd like to manage them so that they both complete enrollment next year. In general, when should people expect for Vertex to start recording sales for chronic pain? We haven't given guidance to that. If you complete enrollment in 2026 for 14-week studies, right, we'll move as quickly as we can. You can add a year on, something like that. We just haven't said. OK. Given the results from the LSR study, what's giving you confidence in DPN and the pursuit of two studies on that now? There has not. We have grand ambitions at Vertex. That's why we went after LSR and still ultimately expect to get there. The drug worked, right? It was the placebo effect that was the surprise there, and the curves didn't separate. I think lessons learned. There are some things that you can do in terms of trial design, in terms of enriching the population or weeding out uber responders or non-responders, et cetera. Pain, you have to have a bit of an iron stomach in pain, given that it is a subjective endpoint. Back to the FDA draft guidance and wanting the most efficient pathway there, it may be LSR next. It may be something else. We're also very, very excited about the work that we're doing in inhibiting NAV1.7s, which actually trigger the pain sensation, and our 1A inhibitor, like Jurnavix, is what propagates it. The idea of combination therapies down the line, which could be synergistic in terms of their effect, that's a possibility as well. We're working quickly to communicate more, but want to make the next best step that's most efficient to get to the full population. OK. Maybe to touch upon the subgroups that you might test for future trials to get a broader label, have any discussions around that topic been advanced yet? Are you primarily focused just on getting through DPN? We had discussions about potential groupings at our end of phase 2 meeting. Those are reflected in the draft guidance that was issued. I think the dialogue will go from there. OK. In terms of the second DPN study, is there any meaningful difference in study design relative to the first one? There is. The FDA endpoint is versus placebo. We have a pregabalin reference arm in the first phase 2 study. We'll just run it versus placebo. Instead of, I think it's 1,100 patients in the first, it'll probably be more like 750 in the second, a smaller, hopefully faster study. OK. In terms of the output of each study, you're expecting them to be equally? That's right. We can combine the results there, et cetera. Yes. OK. Maybe one more. In terms of what you think the pie should ultimately look like, is there any competition on the horizon that would have similar or different mechanisms of action that would influence what potential portions of the pie the company would want to go after? Broadly speaking, we have consistently said that we think it's a specialty commercialization model for acute pain and for peripheral neuropathic pain. Musculoskeletal is a primary care market, so we would partner commercially for that. Within PMP, no, I think we see that in its entirety as a specialty type of market, whether it's endocrinologists or pain specialists, et cetera. OK. With that, let's maybe move on to the pipeline. Let's start with the kidney franchise because there's a lot going on there. You mentioned POVI. We get a lot of questions. We've done a lot of work, and we're excited about IgAN. Can you talk to us about that? That was obviously part of the Alpine acquisition. Can you talk to us about what, because other companies are pursuing this, and at the time Vertex was looking, there would have been a few options to pick from. What in particular about Alpine helped the company decide that that was the platform that you wanted to bring internal? Sure. It was extensive due diligence. It was our largest M&A transaction. I think that we continue to be more and more pleased with, now that was a year ago April, continue to be more and more pleased with how it's all going and where it can go from here. What we were seeking is really a hope for best in class in terms of the clinical profile. Although we have earlier stage data than some peers, we continue to feel that that potential exists there. Fundamentally, we think it's important to inhibit both BAF and APRIL, given they act at different points in the cycle of B-cell maturation. I think the targeted protein design of POVI also, we think, will give it better affinity and potentially potency. It also can lead to smaller molecule size, which is important for the second half of the bucket I'll talk about in a bit. To date, again, earlier phase data, but we have seen the greatest depth of response in terms of reduction in proteinuria, our UPCR. We'd hope to be able to sustain that over time, given that targeted design and the dual inhibition. I think also important to us were the patient-centric factors. Principally, that stems to being able to have an easy-to-use autoinjector for at-home use with smaller volume. Again, that smaller molecule means it's 80 mg, which is smaller volume, so less painful. Also importantly, be able to do it only once every four weeks. I think in more crowded markets, and you've seen this in the past, it's not always the first entrant. It's the entrant that has the best clinical profile and patient-centric factors that can ultimately win in that market. We'd also hope to, I think, a bit in terms of mind share with nephrologists to have some benefit from POVI as a pipeline and a product. Moving forward into a phase 3 in primary membranous nephropathy later this year and gaining that mind share as well with our enoxaparin study. We have accelerated the timelines for POVI in IgAN since the acquisition, starting the trial more quickly and then moving up. We hit the interim analysis enrollment in, we announced that in May, and then saying that we would complete enrollment in the full study by the end of this year. To that point, actually, I'd like to note that in Q3, I think because of the faster enrollment of POVI, because of the increased investments that we're making in marketing initiatives for Jurnavix behind the launch in acute pain and the reimbursement progress we're making, as well as some acquired IPR&D charges due to investments in external innovation, it's likely for the full year 2025, excuse me, that our operating expense guidance with the upper end of the range of $5 billion will exceed that by a slight amount. OK, good to know. You mentioned it's a credit space, potentially credit space. I know you've had three competitors have data readouts. It seems to be a moving target between trying to decide whether April alone is good, April BAF might be better, dosing frequency, and how it's being dosed. You're also in development for trying to develop an autoinjector for home use. That's right. Can you give us an update on where that is and where would that be integrated into the clinical program? Those studies are ongoing, and the expectation is we'll have that at commercial launch. OK. Home use autoinjector, again, small volume, every four weeks. How big does Vertex think that the IgAN opportunity is, the TAM? This is another area where we're expanding both geographically as well. Our belief is that there's probably over 300,000 patients in the U.S. and Europe, and that if you partnered with Xylab for China and surrounding countries and with Ono for Japan and surrounding countries, you can get a patient population well in excess of a million once you count all those other regions as well. In terms of the strategy that was used for CF, how would an IgAN strategy be different in terms of the investment that would be needed for sales force, et cetera? Yeah, so we have a variety of different models, right? Our CF field force is quite small, but there's a large sort of corporate headquarters team that helps patients with reimbursement, et cetera, et cetera. Pain will be the opposite. It's a larger field force. We started with about 150 reps, and we'll probably get closer to 300 over time, but then much smaller, if not an outsourced sort of patient because it's acute patients to date, right? Casgevy is probably more CF-like but a little bit larger. I think with IgAN that principally, we are not a therapeutic category company, but we do have four programs in the kidney space with our 80 PKD therapy, VX-470, excuse me, that has begun its proof of concept study, which is very exciting. We are beginning the work to get ready for a renal sales force. Stay tuned on numbers there. I think it could be quite impactful given what we'd like to call this renal renaissance. Our CEO is a nephrologist and will lament that for many years, it was just repurposed cardiovascular medicines that nephrologists had at their disposal. Now there's really a nice new wave of innovative therapies. I think that will help in terms of mind share, patient reach, et cetera. I think that's partially what's helping drive the faster enrollment in POVI for IgAN, frankly. You talked about other indications. You mentioned PMN. How big is that opportunity relative to IgAN, do you think? It is definitely smaller. I think we'd have a first mover advantage there. Again, it's sort of right there, and same nephrologists treating those patients. I'm forgetting the exact patient number right now, though. Apologies. You also have mentioned GMG and WEHA. GMG, I think most people are more familiar with because of argenx now. Where is the room for improvement there? Yeah, I think that for myasthenia gravis, it is a B-cell-driven disease. We're excited about the opportunity and feel that current therapies, patients may have to cycle on or cycle off, and that you could have sustained chronic therapy and hopefully even more of a transformative benefit with a therapy that controls B cells like POVI. Stay tuned. We said, I think for WEHA, that we'll wait for additional data from the RUBY4 basket study by the end of this year. With myasthenia gravis, we're awaiting ongoing discussions with the agency. More updates post those. OK. Maybe a last couple of questions on dosing frequency for all the different indications. How should we be thinking about that? I think that it's likely, given the advantages of POVI, that you could see that monthly dosing across the indications. That's the early plan, I think, for PMN. For the others, it's just too soon to tell. That would be our hope. OK. Before I let you go, out of all the programs that the company is developing, number one, what should we be most excited about? Number two, what do you think is most underappreciated? We have a rule, no favorite children at Vertex. Both Reshma and I are moms of twins, so we're good at that and maintaining that rule. I think that we do have whether if you want to solve a public health crisis, that's Jurnavix and the opioid crisis. If you want to bring transformative effect to an underserved patient population, that's Casgevy and sickle cell and beta thalassemia, right? If you want to focus on a large patient population that hasn't had targeted therapies, that's IgAN and PMN. I think we really are excited about all of them. I would mention, in terms of what's most overlooked, we didn't discuss the Zomylacell for type 1 diabetes, really exciting opportunity there in a phase 3 study. These patients are on 30, 40 units of exogenous insulin daily, and we see them insulin-independent and free from severe hypoglycemic events. Really exciting technology there. OK. With that, we are out of time. Good time. Thank you, guys, for joining us this morning. We'll talk to you soon.