After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Miss Susie Lisa. Please go ahead. Good evening all. My name is Susie Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our first quarter 2026 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Charlie Wagner, Chief Operating Officer and Chief Financial Officer, and Duncan McKechnie, Chief Commercial Officer. We recommend that you access the webcast slides as you listen to this call. The call is being recorded, and a replay will be available on our website. We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements, including without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, beta thalassemia, and moderate-to-severe acute pain, our pipeline and Vertex's future financial performance are based on management's current assumptions. Actual outcomes and events could differ materially. I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. I'll now turn the call over to Reshma. Thanks, Susie. Good evening all, thank you for joining us on the call today. Vertex is off to a terrific start in 2026, which we see as a year defined by execution. Q1 revenue growth was strong across the portfolio as we reach more patients with more products and delivered total product revenue of $2.99 billion, reflecting 8% growth year-on-year. Importantly, we achieved key commercial milestones for each of the newer products since launch through end of Q1. ALYFTREK exceeded $1 billion in cumulative revenue. More than 500 people have initiated their CASGEVY treatment journey, and over 1,000,000 prescriptions have been written for JOURNAVX. Another highlight in Q1 was that products from the new disease areas, namely CASGEVY and JOURNAVX, drove approximately 25% of total product revenue growth. Execution in R&D was equally strong, with multiple regulatory submissions recently completed and more anticipated, combined with rapid progress across clinical trials and important advancement in research. Let me spotlight a few accomplishments. First, on pove, the interim analysis results from the phase III RAINIER study in IgAN on efficacy and safety from top to bottom were sparkling and further fueled our enthusiasm for pove as a potentially best-in-class BAFF/APRIL inhibitor. I was exceptionally pleased with the rapidity and quality of the recently submitted BLA filing for pove in IgAN. Indeed, at 27 days from database lock to regulatory submission, this was the fastest submission in Vertex history. Equally notable is the urgency with which the pove primary membranous nephropathy and the pove myasthenia gravis programs are advancing. In membranous, the phase II study has been fully enrolled, and the phase III program has already initiated. In addition, the phase II proof of concept myasthenia gravis trial is underway. Second, on CASGEVY, I'm also very pleased with the rapidity and quality of this sBLA submission for CASGEVY in 5-11 year-olds with sickle cell disease or beta thalassemia. The CASGEVY filing has been granted a commissioner's national priority voucher, reflecting the importance of treating this younger age group before some of the most serious complications of the disease can begin. Overall, Vertex continues to extend its leadership in CF, drive growth with new product launches while building out our next disease area franchise in nephrology, accelerate programs in mid and late-stage development, and advance the earlier stage R&D pipeline. Tonight, I'll limit my R&D comments to CF as well as the pipeline programs with the most significant new information to share. Certain renal programs, pove myasthenia gravis, and zimislecel in type 1 diabetes. Starting with CF, four quick R&D updates for this quarter. We recently reached a significant milestone in the U.S. with label expansions for both ALYFTREK and TRIKAFTA. With this expansion, patients with a clinical diagnosis of CF who have at least one variant in the CFTR gene that is responsive based on clinical and or in vitro data are now covered by the ALYFTREK and TRIKAFTA labels, reinforcing the impact of these medicines regardless of the location of the variant in the CFTR protein. This is a significant expansion of eligibility that reflects decades of investment, effort, and a relentless pursuit of the science. It is also a great example of innovation using results from clinical trials complemented by in vitro data to expand the benefit of Vertex CFTR modulators to about 95% of people with CF, including those with rare and even N of one genotypes. As we expand the ALYFTREK and TRIKAFTA labels to additional mutations, we're also expanding the labels to younger patients. We will soon submit for approval for ALYFTREK in patients 2 - 5 years of age, where you may recall our pivotal trial demonstrated a remarkable 65% of children reaching normal levels of CFTR function. We also plan to submit for TRIKAFTA in children 1 - 2 years of age in the near term. In addition, we continue to advance our next generation 3.0 CFTR modulators, including VX-828, which is currently in a study of patients with CF. We are on track to complete the study and share results in the second half of this year. Following closely behind VX-828 in the family of next-gen 3.0 are VX-581 and VX-272, both of which are currently in the clinic in phase I healthy volunteer studies. As we have consistently said, if it is possible to do better in CF, we're committed to being the ones who do so. Finally, on VX-522, the mRNA therapy we've been developing for people who produce no CFTR protein and therefore cannot benefit from our modulators. We previously disclosed tolerability issues in this program. Despite actions we have taken in the trial to overcome these issues, we have not been able to do so. As such, we have chosen to discontinue the program. Given this early termination, we will not be able to assess the efficacy or full safety of VX-522. We will be working with sites to close out the study in the coming weeks. Moving on to our renal franchise, which continues to make quick progress and is rapidly establishing itself as Vertex's fourth franchise along CF, heme, and pain. In total, we have four programs in mid and late-stage development in renal: pove in IgAN, pove in primary membranous nephropathy, inaxaplin in AMKD, and VX-407 in ADPKD. Tonight I'll cover the first three programs, starting with pove in IgAN. Recall pove's differentiated potential best-in-class profile stems from its specific design as an engineered TACI fusion protein with binding affinity, potency, and PK properties that deliver optimal dual BAFF/APRIL inhibition. The dual inhibition and engineering advantage is evident in both the interim analysis data of the RAINIER study, where we saw rapid, deep, and sustained improvement in proteinuria, a favorable safety profile, and consistency across all subgroups, as well as in three key patient dosing benefits: once-monthly dosing, small volume, and subcutaneous administration via an auto-injector. Overall, the phase III interim analysis data represent a home run in terms of study design, execution, and the results, with pove achieving statistically significant and clinically meaningful results across all primary and secondary endpoints. Patients in this trial received excellent standard of care with high rates of background medicines, including the highest rates of SGLT2is seen in any IgAN study. Baseline characteristics were well-matched to real-world IgAN patients in terms of age, renal function, and degree of proteinuria. In addition, as a measure of study quality, it's important to look at discontinuations. In this study, treatment discontinuations were low, and trial discontinuations were even lower at a rate of 1.5% in the placebo group and 0.8% in the pove group. To replay the top-line primary and secondary efficacy results. For the primary endpoint, pove achieved a 52% reduction from baseline in proteinuria as measured by 24-hour UPCR. That's a 49.8% reduction versus placebo. For the first secondary endpoint, pove treatment led to a 77.4% reduction from baseline in serum Gd-IgA1 levels. That's a 79.3% reduction versus placebo. For the second secondary endpoint, of those patients with hematuria at baseline, 85.1% of pove-treated patients achieved hematuria resolution, which is a 61.7% reduction versus placebo. In addition, 42.2% of patients reached the exploratory endpoint of 24-hour UPCR of less than 0.5 g /g, an important clinical threshold. These are remarkable results, and particularly noteworthy considering that at the time of the interim analysis, patients had received just 36 weeks of pove treatment. On safety, pove was generally safe and well-tolerated. The majority of adverse events were mild to moderate, and there were no serious adverse events related to pove. Importantly, in terms of infections, most were mild to moderate. The rate of SAEs of infection was low at 0.5%, observed in both the placebo and pove groups. There were no opportunistic infections and no discontinuations related to pove overall, including no discontinuations due to infections. Lastly, on anti-drug antibodies or ADAs. ADAs were observed as expected with biologics had no impact on pove's efficacy or risk profile. We look forward to sharing more details of the interim analysis results and anticipate doing so at upcoming medical meetings this fall. Shifting to pove in primary membranous nephropathy. I am pleased to share we have completed enrollment of the phase II portion of the OLYMPUS phase II/III study and have already initiated the phase III portion ahead of our previously announced mid-2026 goal. Finally, on pove, as part of its pipeline and a product potential for B cell-mediated diseases beyond renal. I'm also pleased to share that the phase II proof of concept study of pove in generalized myasthenia is underway. This is a 30-patient study of people with gMG evaluating both the 80 mg and 240 mg dose for 12 weeks, with the primary endpoints of safety and the percent change from baseline in IgG at week 12. The rationale for studying pove in myasthenia is compelling. It's a serious B cell-mediated disease with high morbidity affecting approximately 175,000 people in the U.S. and Europe. There is high unmet need as current therapies have meaningful limitations, which means there's room for improved efficacy, a better benefit/risk profile, and more patient-friendly dosing and administration, which we have discussed in the context of IgAN as being critically important when considering a chronic biologics market. We believe pove's mechanism of action, striking at the heart of autoantibody production with an engineered protein format, provides best-in-class promise in myasthenia, and we are excited to develop this opportunity. Shifting back to renal to finish up with inaxaplin in APOL1-mediated kidney disease or AMKD. First, on AMPLITUDE, the pivotal phase III study of primary AMKD, that is to say, patients with two APOL1 variants, proteinuria kidney disease, and no other renal-related comorbidities. We are on track to conduct the interim analysis, which occurs after 48 weeks of treatment, and to share data from this cohort in early 2027. If positive, we will be poised to file for potential accelerated approval in the U.S. thereafter. Second, on AMPLIFIED, our phase II-b study of inaxaplin in separate populations. Patients with two APOL1 variants, modest proteinuria, and no other kidney disease, and patients with two APOL1 variants, moderate to severe proteinuria, and a second disease, type 2 diabetes, that could impact the kidney. These two populations are not being studied in AMPLITUDE. We recently completed enrollment in the AMPLIFIED study, which is a study of 13 weeks in duration. Given the clear differences in these populations, we made the decision early on to study them in separate trials. Emerging data in the field confirm the wisdom of this decision. We are excited to learn from the AMPLIFIED study and look forward to sharing results in the second half of this year. Finally, on type 1 diabetes, a reminder that zimislecel has very strong clinical results to date, as detailed in last year's The New England Journal of Medicine. Among patients who received a full dose and had at least one year of follow-up, 10 out of 12 patients were insulin-free. These results are unprecedented and are particularly noteworthy given that these patients are those with 20+ years of type 1 diabetes, undetectable endogenous insulin production at baseline, taking 40+ units of exogenous insulin per day, and with two or more severe hypoglycemic events per year despite best available care. You may recall that in the second half of last year, we paused dosing of the phase I, II, III study in order to conduct a manufacturing analysis, which we have now completed. I am pleased to report that dosing in the study has resumed and multiple patients have been dosed. With dosing now restarted, we will update you in the coming months on the revised timelines for study completion and regulatory filings. With that, I'll turn the call over to Duncan for a commercial update. Thanks very much, Reshma. I'll start with CF, which continues to perform very well. Year-over-year revenue growth was 6% globally, balanced nicely between U.S. growth of 5% and international growth of 8% in quarter one. Global growth reflects continued ALYFTREK uptake as its once-daily dosing and improved sweat chloride profile continue to resonate with the clinical and patient communities. As mentioned, ALYFTREK has now surpassed $1 billion in cumulative global revenue since its approval in the U.S. in late December 2024 and Europe in July 2025. Outside the U.S., we have signed reimbursement agreements in 11 countries for ALYFTREK in quarter one alone, building on the access generated in the second half of last year. The tremendous scientific and regulatory achievements represented by the label expansions for ALYFTREK and TRIKAFTA also represent a meaningful incremental commercial opportunity of approximately 800 people in CF who are newly eligible in the U.S. This broad labeling is one of several key CF growth drivers for the remainder of 2026, along with the global rollout of ALYFTREK, treating younger patients, and expanding into additional geographies. We have worked closely with the CF population for two decades and remain focused on continuing to serve the CF community and expand our leadership across all genotypes, age groups, and geographies. Shifting to heme, the rollout of CASGEVY continues to gather momentum across all three regions, and I'm pleased to highlight another significant commercial milestone since launch. Over 500 patients have now initiated the CASGEVY treatment journey. Hundreds have had their first cell collection, and many patients have had their cells edited and are ready for infusion. During the first quarter, we delivered $43 million in CASGEVY revenue. Importantly, we worked on securing a pricing agreement for CASGEVY in Germany in quarter one and are currently working through the implementation steps. This is a historic moment, and we're excited that German patients with sickle cell disease and TDT may soon be benefiting from long-term access to CASGEVY at a sustainable price. Overall, we are very encouraged by the robust flow of patients in the U.S., in Europe, and the Middle East moving from referral to cell collection and infusion. First quarter revenue reflects expected variability quarter- to- quarter as patients choose the timing for their infusion that suits them best. For the full year 2026, the CASGEVY outlook is very promising as we have built our ATC network, secured reimbursements, and now have many patients at all stages of the treatment journey. We therefore have very strong visibility to revenue for the rest of 2026 for CASGEVY to contribute meaningfully to our $500,000,000+ revenue goal for non-CF products this year and towards CASGEVY's ultimate multi-billion dollar potential. For JOURNAVX in moderate-to-severe acute pain, prescriptions, prescribers, and awareness all continue to build. More than 350,000 prescriptions were filled in the quarter compared to approximately 550,000 in all of 2025, which was in line with our expectations. We also surpassed the milestone of over 1,000,000 JOURNAVX prescriptions written since launch. Prescriptions this quarter were once again split roughly 50/50 between the hospital and retail channels and generated $29 million in revenue, also in line with our expectations. Overall, prescription growth remains strong, although quarter one revenue reflects some normal inventory destocking. We remain on track to more than triple the 550,000 prescriptions from 2025 and for revenue growth to significantly exceed prescription growth. I'll now outline some of the key drivers of our continued growth and expected success for JOURNAVX in 2026. Firstly, physician and patient clinical experiences on JOURNAVX continue to be excellent, which provides a great foundation for continued growth. We also continue to see outstanding breadth of physician uptake as well as JOURNAVX additions to hospital and IDN formularies, protocols, and order sets. We continue to make good progress in the payer space with 240 million lives now covered. In addition to the big three commercial PBMs, I'm delighted to announce that we've reached an agreement with the first of the big four Medicare Part D plans to start covering JOURNAVX effective as of May 1st. Given the multiple and well-documented challenges that opioids present seniors, this is welcome news. We're in discussions with the remaining Medicare Part D plans as well as the smaller regional plans. We have completed doubling the size of our field force to 300 representatives, slightly ahead of plan. As we've communicated before, JOURNAVX is highly promotionally responsive. We're excited about the impact of this new field team on JOURNAVX growth. Lastly, we also continue to execute multiple initiatives to drive awareness, growth, and provide new mechanisms for patient access, including the launch of Vertex Pharmaceuticals's first direct-to-patient telehealth platform, Informed Pain Care. This platform is accessible from journavx.com and provides appropriate and independent telehealth evaluations for non-surgical acute pain patients if eligible. We are also pleased that JOURNAVX was recently added to the list of non-opioid medicines eligible for separate payment under the NOPAIN Act, effective retroactively to January 23rd. In summary, with the increased size of our field organization, our continued progress in securing payer and hospital coverage as well as strong gains in formulary status, we remain confident we will triple prescriptions for JOURNAVX in 2026. In addition, our strong reimbursement progress continues to position us to taper our patient support program over the course of 2026 and enter 2027 with a normalized gross to net. We continue to expect JOURNAVX to contribute meaningfully to the $500,000,000+ we expect in revenue outside CF this year. I'll conclude with an update on the commercial initiatives for our emerging renal business. We're investing in the nephrology community for the long term, and povetacicept is the first in a series of potentially transformative medicines that tackle the underlying cause of four serious renal diseases, namely IgAN, pMN, AMKD, and ADPKD. We were thrilled with the interim analysis results of the RAINIER phase III study with excellent results across the board in efficacy, safety across all subgroups, and in the areas of greatest interest to nephrologists and patients. The results create a superb foundation for the commercial launch of a potentially best-in-class medicine. Our goal for povetacicept is to be physicians' first choice for their IgAN patients given pove's compelling trifecta of differentiated efficacy results, well-tolerated profile, and patient-centric administration characteristics due to its low volume monthly dosing via subQ auto-injector. Based on our market research and discussions with nephrologists plus feedback from our field team engagements, we know nephrologists are looking for treatments in IgAN that meaningfully and rapidly reduce proteinuria in the patients they treat, as they see proteinuria as the key indicator of where the patient is headed clinically. Nephrologists also seek a favorable tolerability profile, and both physicians and patients communicate to us the need for a seamless treatment experience, which includes everything from access to patient support to monthly dosing, size of dose, and administration in an auto-injector. We believe that uniquely, pove has the clinical profile and that Vertex has the capabilities to meet all of these needs. Our renal field force will be specialty-sized and large enough to cover nephrologists who see approximately 80% of U.S. IgAN patients. We will target key facilities that represent a combination of renal centers of excellence, glomerular disease clinics, and key high-volume private practices. Our payer conversations are proceeding well in a U.S. market where approximately 70% of patients have commercial coverage. We have a proven track record in securing broad and rapid access for our medicines and plan to establish the same for pove and IgAN. Lastly, we know that the quality of the patient support provided is critical in the biologic space. With that in mind, Vertex programs to support pove patients will enable speed to therapy and personalized support through the treatment journey, delivering a seamless experience of onboarding for patients and physicians alike. Pove in IgAN is the first component of our emerging renal franchise. We're excited to bring it to nephrologists and their patients. Based upon our work with them, we know they're excited to try it as well. We believe pove delivers exactly what nephrologists are looking for in IgAN. Just as we've done for over a decade in CF, pove's success will be driven by a field force delivering a high science sell fueled by a potentially best-in-class product, broad reimbursement, and robust and high-quality patient programs. We are very excited to begin building our fourth commercial pillar and creating another multibillion-dollar franchise at Vertex. I'll now turn the call over to Charlie to review the financials. Thanks, Duncan. As Reshma noted, Vertex's Q1 2026 results demonstrate our consistent strong performance and attractive growth profile. First quarter 2026 total revenue increased 8% year-over-year to $2.99 billion. CF global revenue increased 6% year-over-year, and new disease areas also contributed with CASGEVY delivering $43 million and JOURNAVX $29 million in Q1 sales, representing about 25% of total year-over-year growth for the quarter. By region, U.S. revenue growth of 7% year-over-year was driven by continued steady performance in CF and growing contributions from CASGEVY and JOURNAVX. International revenue grew 9% year-over-year, driven by continued CF expansion and increasing contribution from CASGEVY, and as anticipated, a benefit from year-over-year changes in foreign exchange. First quarter 2026 combined non-GAAP R&D acquired IP R&D and SG&A expenses were $1.29 billion, an increase of 5% compared to $1.23 billion in the first quarter of 2025. Within total OpEx, non-GAAP R&D expenses were down 2% year-over-year, partly driven by the timing and mix of certain clinical trial expenses. In addition, certain pove manufacturing expenses were included in R&D in 2025 and are now recorded in cost of sales following the positive interim analysis data. Non-GAAP SG&A expenses increased 30% year-over-year, driven primarily by commercial investments, with roughly 40% attributable to JOURNAVX in pain and approximately 1/3 to renal launch programs. We also recorded $1 million in IP R&D expense in the quarter versus $20 million in the first quarter of 2025. First quarter 2026 non-GAAP operating income was $1.31 billion compared to $1.18 billion in non-GAAP operating income in the first quarter of 2025. First quarter 2026 non-GAAP effective tax rate was 19.6%. First quarter 2026 non-GAAP net income was $1.1 billion, an increase of $93 million compared to the first quarter of 2025, primarily due to increased product revenue, partially offset by increased operating and income tax expenses in the first quarter of 2026. First quarter 2026 non-GAAP earnings per share were $4.47 compared to $4.06 in the first quarter of 2025, reflecting our strong revenue growth and disciplined expense management. We ended the quarter with $13 billion in cash and investments after deploying approximately $344 million to repurchase more than 741,000 shares in the first quarter. This activity reflects our ongoing commitment to returning value to shareholders while maintaining the flexibility to act on strategic growth opportunities. Overall, our priorities for cash deployment remain unchanged with a primary focus on investing in innovation. Switching to guidance. We are reiterating our 2026 total revenue guidance of $12.95 billion-$13.1 billion, representing growth of 8%-9%. This outlook reflects continued solid performance from the CF franchise driven by the ALYFTREK launch, expansion into younger patient groups, incremental patients from the label expansion, and geographic expansion. We continue to have high confidence in our outlook for revenue of $500 million or more from non-CF products driven by growing CASGEVY infusions, where we have good line of sight given the length of the patient journey and a meaningful ramp in JOURNAVX prescriptions and revenue as gross to net normalizes through the second half of the year. Our revenue outlook continues to include an expected impact from foreign exchange net of our hedging program. Our outlook for full year gross margin remains at just under 86%, reflecting the growing non-CF product mix impact and ongoing investments in manufacturing network and process development for various products. We are also reiterating our combined non-GAAP operating expense guidance of $5.65 billion-$5.75 billion, reflecting continued investment in our late-stage clinical pipeline and commercial infrastructure and activities for new launches and revenue diversification. We also continue to expect our non-GAAP effective tax rate to be in the range of 19.5%-20.5% for the full year 2026. On the subject of tariffs, we do not expect any material impact to the income statement in 2026. We continue to evaluate the details of recent announcements and the potential applicability to Vertex. In summary, Q1 2026 was a very strong start to the year. Financial results are on track. Commercial launches and diversification are gaining momentum. We continue with targeted investment both in innovation and commercialization as the pipeline is advancing across our multiple disease areas. Our increasingly diversified commercial portfolio, now spanning three disease areas and soon to be four with the establishment of the renal franchise, is driving new revenue streams and adding to our near and long-term growth profile. Vertex is well-positioned to continue expanding its impact for patients, investors, and all stakeholders. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls. I'll now ask Susie to begin the Q&A period. We will now begin the question-and-answer session. To ask a question you may press star then one on your touchtone phone. If you're using a speaker phone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Our first question for today will come from Jessica Fye with JP Morgan. Please go ahead. Hey, guys. Good afternoon. Thanks for taking my question. You've talked about renal one day rivaling the cystic fibrosis business in size. Can you speak to what needs to play out from here to realize that vision? Among your renal assets, which you see having the greatest long-term revenue potential? Thank you. Hi, Jess. This is Reshma. I guess as a nephrologist at the company, maybe I can take this and Duncan, please feel free to add. Jess, what we're talking about in our emerging renal franchise is four diseases, three assets. Pove for IgAN, pove for membranous, inaxaplin for AMKD, and what we call VX-407 in ADPKD. The reason I think that this has the potential to be as big, if not larger than CF is that the diseases that these medicines treat are rare diseases, but they are common rare diseases. When you add them all up together, they are well into the hundreds of thousands of patients. For example, we talk about 150,000 or so patients with IgAN in North America and Europe, 100,000 patients with membranous in the same geographies. For AMKD, that's another 150,000 or so patients with the AMPLITUDE population, not including the AMPLIFIED population, which adds another 100,000. ADPKD is about 300,000 patients. Of course, the first medicine that we're studying, VX-407, can treat about 10% of that 300,000. One, while each one is a rare disease, they are common rare diseases, and when you add it together, we're at hundreds of thousands of patients in just the Western world. The second is that in renal medicine, unfortunately, the outcome of these diseases is a relentless decline in renal function and a movement then to death, dialysis, and transplantation. Obviously, those are enormous burdens for society. I don't need to say much more about death, but dialysis, in particular, is exceptionally expensive. While it allows you to live, it is a very, very difficult life, and life expectancy is like a very serious cancers like pancreatic cancer. Last of that block, when we look at the emerging results for pove, for example, in IgAN and membranous, you can look at the phase II, and for IgAN, you can certainly look at the phase III interim analysis results. As I said on the call, they are sparkling from top to bottom, safety, efficacy. These are the kind of medicine that can bring transformative value. When I think about AMKD, same thing. You look at the phase II results that we published in the New England Journal, 47.6% reduction in proteinuria is a very big deal. When we think about ADPKD, no human results yet. When you look at the mechanism of action, this is to say to properly fold the misfolded PC1 and what we see preclinically, another one where we think transformative effect. That's why we believe this is another vertical that can rival, if not crest CF. Best renal asset. That's a tough one, Jess. I'm gonna focus my attention for the here now on pove. It just looks sparkling. You can call it near term bias because we just looked at the phase III results. Thank you. The next question will come from Salveen Richter with Goldman Sachs. Please go ahead. Good afternoon. Could you discuss the read-through from Maze's recent data to the inaxaplin program? Also, could you just speak for that program whether there were enrollment considerations to enrich for patients with larger APOL1 contribution to CKD, especially in the non-FSGS patients? Thank you. Yeah. Hey, good afternoon, Salveen. On the Maze data, you know we don't like commenting on other companies' assets and results, but I'll simply say at the top line, the Vertex results were 47.6% reduction in proteinuria, as published in The New England. My recollection of the Maze data is 35.6% at the top line. Going below that is difficult because we're talking about groups of two and three patients with or without diabetes and such, and I just don't think you can make very much when you're down to two or three patients. What I will say is I'm very happy about the decision we made early on to not mix a heterogeneous group and to focus our program on those with heavy proteinuria, two APOL1 alleles and reduced kidney function and not study those who have a comorbid condition like diabetes. Instead, what we did is study those people in a separate trial called AMPLIFIED, along with a group of patients with lower proteinuria. That trial is done enrollment, and I do expect to have results in the second half of this year. The next question will come from Brian Abrahams with RBC Capital Markets. Please go ahead. Hey, guys. Thanks so much for taking my question. With the pove launch not too far off, what do you think you'll need to convey to KOLs and community physicians to convince them of povetacicept's differentiation and overcome first mover advantage by competitors? Thanks. You bet, Brian. Let me ask Duncan to take that. He's been spending a lot of time with nephrologists, both in academic institutions and centers of excellence as well as in the community. Duncan? Brian, good afternoon. One comment before we dive into your answer. I just made the point that obviously this is a huge market opportunity. There's about 160,000 patients in the U.S. It's 5 x bigger than CF, for example. The vast majority, about 75% of those patients are nowhere near the KDIGO guideline goal in terms of proteinuria, the opportunity is significant. We've been engaging through market research and other mechanisms with many nephrologists, essentially they tell us they're looking for a product that significantly impacts proteinuria, we'll come back to that, is well-tolerated and is easy for patients to use. We believe that povetacicept uniquely meets those needs. We think it has the sort of winning trifecta of incredible clinical effects, as you heard in the prepared remarks, things like the rapid, deep, and sustained reduction in proteinuria, as well as Gd-IgA1 and hematuria. It has a supremely favorable tolerability profile and very attractive dosing and administration. As you know, it's once a month, it's a small volume dose, and it's delivered by an auto-injector. We think we have an incredible product, as we saw in the clinical data. We also know from our market research that those nephrologists that distinguish between BAFF/ APRIL and APRIL alone, the vast majority of them prefer dual inhibition with BAFF and APRIL. In our patient market research, the vast majority of patients prefer monthly dosing over weekly dosing. In fact, 8x more patients prefer monthly dosing to weekly dosing. In terms of the profile of the product matched against the needs of the physicians and patients, we think we have a best-in-class asset on our hands. I would also add on the commercial capability side, we know how to execute a high science sell. We know how to secure rapid, deep, and broad reimbursement, and we know how to build patient support programs, which are incredibly important in the biologic space, as we have done for the last 12, 13 years or so in cystic fibrosis. We're feeling really good about the profile of povetacicept. We are getting ready for launch, and we're going to be ready to go the day the FDA give us regulatory approval. The next question will come from Geoff Meacham with Citi. Please go ahead. Good afternoon, guys. Thanks so much for the question. I have two quick ones. On pain and on VX-993 in particular, you know, as you guys have got commercial experience with JOURNAVX, are there settings where an IV modality is perhaps a better fit in the clinical practice? I imagine that's maybe the hospital setting in the queue, but wanted to obviously get your perspective. On pove, you know, congrats on the quick filing in IgAN, but looking beyond pMN and gMG, you know, is it worth it to do a basket study? Are there other autoimmune indications that make, you know, sort of the most differentiation for pove and then maybe have the highest probability of success? Thank you. Hey, Geoff, this is Reshma. On, on the pain portfolio and, whether or not an IV medicine would be helpful, I think it would be helpful to have an IV medicine. What we're really looking to do here, and the reason we have, not only suzetrigine or JOURNAVX, but VX-993 and additional NaV1.8s, but very importantly NaV1.7s, is to make sure that we have the best medicine, whether it's PO or IV, and that formulatability into IV is one of the features that we're looking at and are interested in. Switching then to, pove and where we see things go, IgAN is already done in terms of the interim analysis and filing. Membranous p hase III is already underway. Myasthenia phase II is underway. There are some additional B cell- mediated diseases that we are thinking about. I do think a basket study is a very efficient way of evaluating those conditions through phase II development. I won't state much more about exactly which conditions. Suffice it to say, there are some B cell- mediated conditions where autoantibodies are important, where we think pove would fit nicely. I do think that going about this by way of basket studies and efficient phase II/III are the right way to go. You'll be hearing us talk more about pove and our immunology portfolio in the coming months and in the coming time. I like your idea. Thank you, Reshma. Yep. Yeah. The next question will come from Cory Kasimov with Evercore ISI. Please go ahead. Hey, good afternoon, guys. Thanks for taking my question. I wanted to follow up on Salveen's question on inaxaplin. When you think about the pending data from AMPLIFIED, looking at AMKD patients with moderate proteinuria or diabetes, what's needed in this population for a clinically meaningful benefit to justify advancement in this patient segment? Thank you. Cory, I would say that generally speaking in renal medicine, we've been thinking about double-digit improvements as being valuable. By that I don't mean 10% or 11%. I would say if we can show a 30% improvement, you know, some number between 20% and 40%, 25% and 50%, some substantial double-digit improvement in proteinuria on top of standard of care, of course. On top of ACEi, ARBs, SGLT2i, et cetera, that would be meaningful. We'll be able to see how we fare shortly. The enrollment's done. It's a 12-week study, we'll be able to tell you the results in the near term. That's very helpful. Thank you, Reshma. You bet. The next question will come from Michael Yee with UBS. Please go ahead. Hey, this is Michael Yee from UBS. On pove, do you believe that on the efficacy standpoint, that your differentiation on eGFR will be able to come through over nine, 12 or 24 months versus, say, Otsuka, which I think is presenting their eGFR nine-month data, I think next month, and then their two-year data coming up. I just wanted to think about where you would start to see differentiation for yours in a read-through to their data that they're gonna present. Then on the safety component for pove, Reshma, can you talk a little bit about the hypogammaglobulinemia? I think there are some questions around whether 150 or 300 matters and the noise within the assay and the timing of the measurement and why you don't think that will be any issue here for pove. Thanks. Yeah. Start with safety and the question on hypogammaglobulinemia. Then we'll go to efficacy. On safety, the results are really terrific. Because pove and any medicine that works on APRIL or BAFF/APRIL, in essence, is modulating B cells, you do need to think about the safety profile. In the safety profile, the domain to think about is infection. Specifically, what we focused on and what I was very pleased to see is we can get this level of efficacy on proteinuria, on hematuria, on Gd-IgA1, on getting down to these very low levels, less than 0.5 g/g, which is the important clinical threshold. We can get down to those levels with a very favorable safety profile. On infection, most of the infections are mild to moderate. Think upper respiratory infection. There's no opportunistic infections, no uncommon infections. The SAEs of infection are low and balanced. It's exactly 0.5% in the placebo group and the same exact number in the pove-treated group. That looks really nice. With regard to the actual immunoglobulin levels, let's focus on IgG. The IgG levels of less than 300 or 150 or 200, some people use 400. These thresholds are important because that's how people set up their trials, that's how the trials may have certain actions taken. You are correct. Each trial defines a different threshold. You measure it a different number of times. Some people measure it monthly, like us. Other people measure it quarterly. Some people require multiple measurements to call it less than that threshold. Others require a simple one level. It's not very easy at all to cross-compare. The important thing, though, Michael, if you're asking me, "Hey, is there anything there that gives you concern?" None at all. The important thing to look at is the infections, and the infections look very balanced between these groups. On efficacy, you ask about GFR, which is the regulatory enabling endpoint, right? The regulators have said proteinuria is acceptable at nine months for accelerated approval, but they are looking for two-year GFR for full approval. Note, however, GFR is actually not the hard endpoint in renal medicine. The hard endpoint is death, dialysis or transplantation. That's what we're really trying to avoid. It's just that that endpoint takes a long time, the acceptable regulatory enabling endpoint for full approval is GFR. The reason I think that the proteinuria is so important is when you think about that hard endpoint of death, dialysis, and transplantation, okay, if I got one point of proteinuria improvement more than any other medicine, two points, five points, 10 points, compound that over years, and you start to see why proteinuria is so very important. The agency has said very clearly that we're not allowed to share GFR, but they've equally said that they need to see GFR to provide accelerated approval. What I would say is any medicine in IgAN that gets accelerated approval has the proteinuria that we've already shared and has a GFR that the agency finds comforting. Yep. Thank you. The next question will come from Tazeen Ahmad with Bank of America. Please go ahead. Hi. Good afternoon. I wanted to ask what your thoughts are, Reshma, on the read-through from this positive IgAN study that you provided the top line for recently onto the pMN study that you're currently running for pove. Secondly, on the CF pipeline, I just wanted to get a sense of what data you plan on showing in the second half of the year for VX-828 and what would be considered good data there. Thanks. Okay. Let's do IgAN first. Tazeen, I see the some data that are from the IgAN as very important and positive for membranous because now we've studied hundreds of patients over a nine-month period, which is additive information to the phase II results. Things like PK, PD, the reduction in proteinuria. I see all of that in terms of efficacy as important. Clearly, the autoantibody of interest is different. One is PLA2R. That's what we're looking for in membranous versus Gd-IgA1. That has to play itself out. In terms of those other parameters, I see that as really positive. The other variable that I see as very positive is on safety. The fact that there is such a favorable safety profile I see as a positive. The IgAN study was at 80 mg. In the membranous study, we're studying both 80 and 240 to PC1. Lastly, I feel very good about the way the study is being conducted. That is to say, low discontinuations in terms of study discontinuations and treatment discontinuations. I also feel really good about the background therapies. Very important to look at as you think about doing these studies in contemporary practice. Switching now to CF, the VX-828 results are a CF cohort after we've completed the healthy volunteer study. What you should see is data from the single dose that's gone into the patient cohort, and you should expect to see sweat chloride results and safety results as well. It's a small cohort, you shouldn't expect anything on ppFEV1. The readout, the efficacy readout that we're looking for is sweat chloride. You should expect us to share that. The next question will come from Evan Seigerman with BMO. Please go ahead. Hi, guys. Thank you so much for taking my question. I want to expand a little bit on the discontinuation of VX-522. Anything else you can share on the tolerability issues? Then looking ahead, do you plan to utilize another technology to help these patients that are not currently treatable with your current portfolio? Thank you. Good afternoon, Evan. On VX-522, what I can tell you is that the tolerability issue that we have been monitoring and sharing with you now that the study is being discontinued, has to do with lung inflammation, like an inflammatory response, probably in response to the LNP that's being used to deliver it. I say that because this is not unusual in that regard. With regard to what are we gonna do for our patients, I wanna be clear about the fact that our commitment to CF is absolute and steadfast. If there is any more that we can do for our patients in the 95% group, we're gonna be the ones who do it. For our last 5,000 or so patients, we're going to work on that as well. I expect that the challenge is going to continue to be delivery. In terms of modalities, we're going to have to go back to the drawing board on modalities. These last 5,000 are going to require some nucleic acid therapy, right? Because they simply don't make any protein. The big question is not necessarily what the nucleic acid therapy is. We have some big ideas there, and I think, obvious. How do you deliver it without having this lung irritation? That's what we're going to be working on. Great. Thank you. You bet. The next question will come from David Risinger with Leerink Partners. Please go ahead. Yes, thanks very much, and thanks for all the updates. My questions are on JOURNAVX. Could you maybe help reconcile the $29 million in revenue in the first quarter with the volume of either prescriptions or pills? Given that JOURNAVX has PBM coverage for 240 million lives now, which is over 2/3 of the population, does JOURNAVX need to achieve more employer opt-ins and more Tier 2 formulary positions for the gross to net to normalize? Thanks so much. Duncan, do you wanna take that one? Sure. Good afternoon, David. In terms of the first part of your question, I would say overall, by the way, we are extremely pleased with the progress on JOURNAVX. We are fully on track in terms of our prescription numbers and our revenue numbers. In terms of reconciling quarter one dollars and volume, as I mentioned in the prepared remarks, we did see a small but relatively normal channel inventory destocking in quarter one between quarter four 2025 and quarter one 2026. It's also true that in that quarter, of course, Medicare Part D plans are resetting, which can lead to higher co-pays and more abandonment. Also, we saw the traditional reduction in the number of elective surgeries in January, which were a little bit harder impacted this year because of the sort of fairly strong flu season. Overall, I would say that the quarter one performance was in line with our expectations. We are absolutely on track to more than triple the number of prescriptions that we delivered in 2025. To answer the second part of your question, we have just achieved our 240 million lives covered. As you know, we're very happy with that. Actually, in an update since we finalized the script, you know that we've been working on four Medicare Part D plans, and in the script, we communicated that we had secured coverage at one of those four plans. We've actually secured coverage at two of those four plans and are very close to securing coverage at a third of those plans, or the third of those plans. That coverage starts from between May 1st to July 1st. I don't think we need to be focused on downstream plans and employer plans. As we have said all along, as we secure the final pillars of access, the patient support program will taper down. Our gross to net will normalize by the end of the year, and you will see revenue significantly accelerate and accelerate faster than prescription growth as we go through the balance of the year. Thank you. The next question will come from Terence Flynn with Morgan Stanley. Please go ahead. Great. Thanks. Just two questions for me. I was just wondering if you can tell us if there's a defined percentage of FSGS patients in the AMPLITUDE phase III trial for inaxaplin. If there's a cutoff or if you're just pretty much all comers and that mix will be dictated by who's enrolled. For ALYFTREK, just curious to know if you're seeing anything different in terms of patient mix this quarter versus prior quarters in terms of the three different buckets that you guys have focused on. Thank you. Terence, I'll take your FSGS question for phase III inaxaplin, then I'll turn it over to Duncan. I won't be able to share what the baseline characteristics look like because we haven't looked at those data and we don't know those data. What I will tell you is that what's common in AMKD is because they tend to be heavily proteinuria. We're talking about people who are coming in with proteinuria of 0.7 g or more. They often tend to have a biopsy because that's a lot of proteinuria, and people are trying to figure out whether there's an underlying identified cause. It wouldn't surprise me at all if many, maybe even the majority of patients in the AMKD phase III AMPLITUDE trial actually were known FSGS patients because a lot of these patients actually do get a biopsy. Not all of them, but it's not an uncommon act. That would be my guess, but I don't have a formal answer for you. Fortunately, the IA enrollment is complete. The full study enrollment will complete this year, and we fully expect to have results from the IA in early 2027. We'll know the answer real soon. Duncan, ALYFTREK characteristics transition, new. Yeah. Yep. Terence, thank you for the question. Yeah, I'm assuming the three categories you're talking about are the naive patients, the discontinued patients, and the transition patients. I would say that we see continued strong progress in all of those. Once we have both regulatory approval and reimbursement, we see the naive patients coming on first, then we see the discontinuation patients coming on, and then finally, the transition patients are moving onto ALYFTREK, indeed exactly as we desire. At this point, essentially, I would tell you that all new patients are going on to ALYFTREK. No one is going on to TRIKAFTA. They're all going on to ALYFTREK. We see the discontinued patients largely moving on to ALYFTREK, and the vast majority, of course, of our patients now are transitions from TRIKAFTA to ALYFTREK exactly as we would expect. The three drivers really of ALYFTREK growth this year are continued uptake in the U.S., more European countries securing reimbursements, and the expanded labels, for example, the additional 800 patients that were recently included in the most recent labeling updates. Hopefully that answers your question, but we're seeing essentially a similar profile to that which we saw before, and super happy that we are well over $1 billion on ALYFTREK at this point. One more question, please, Chuck. The next question will come from Ellie Merle with Barclays. Please go ahead. An efficacy or safety perspective. I guess as you think about the CF landscape broadly, how are you thinking about sort of the bar set by ALYFTREK versus where you see room for incremental improvement? Thanks. Ellie, we couldn't catch the first part of your question. Would you restart, please? Sure. Sorry about that. Let me know if you can't hear me now. Yeah. You can hear me? Okay, good. Just on VX-828, just to follow up on the earlier question, I guess, what are you seeing as a bar for what you would wanna see to bring this forward from an efficacy or safety perspective? Then just as you think about the cystic fibrosis landscape overall, how are you thinking about sort of the bar set by ALYFTREK versus where you see room for improvement? Thank you. When we had TRIKAFTA and were working to see what the unmet need was, honestly, Ellie, it was a little bit easier to see. As amazing as TRIKAFTA is, we could see that a once-daily medicine would be better for patients. We could see that getting more CFTR protein function, that's to say more sweat chloride, more patients below the diagnostic threshold of 60 and the normal level of 30 would be advantageous. Fast-forward to where we are today with ALYFTREK, genuinely, there is very little unmet need. It's gonna take something special for us to advance, and that's why we're looking at VX-828, we're looking at VX-581, and we're looking at VX-272 because we wanna really interrogate to see if there's more that we can bring to the table. What I'm really saying in the, in the event it's unclear, is this. Today, 90% of people, which you start at a young age, which ALYFTREK is now approved down to six years old, and we're filing for 2 - 5 years old, 90% are less than 60. Two-thirds of our patients are at sweat chloride that's below normal. This is with a once-a-day medicine. Now when you think about it, everyone as Duncan described, all our new patients, all our young patients are coming onto ALYFTREK, there's very little room for improvement here. If it's possible, we're gonna be the ones who do it, but it's getting really, really tough because we're already down to once a day, good-looking DDIs, excellent sweat chloride function with 2/3 normal. It's tough. If we see it, we'll certainly let you know, but that's why we're being so particular in bringing these number of medicines forward to see if anything can be better than ALYFTREK. Great. I think we'll wrap there. Chuck, can you give the replay information? Will do. This will conclude our question-and-answer session as well as our conference call for today. The conference has now been concluded. Thank you for attending today's presentation. A replay of today's event will be available shortly after the call concludes by dialing 1-877-344-7529 or 1-412.