Vertex Pharmaceuticals Incorporated

Good day and welcome to the Vertex Pharmaceuticals first quarter 2026 earnings call. All participants will be in a listen-only mode. Should you need assistance, please signal conference specialists by pressing the star key followed by zero. 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 Ms. 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, and 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. Aliftrek exceeded $1 billion in cumulative revenue. More than 500 people have initiated their Kastjevi treatment journey. and over 1 million prescriptions have been written for Jurnavix. Another highlight in Q1 was that products from the new disease areas, namely Kastchevy and Jurnavix, 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 POVI, 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 POVI as a potentially best-in-class Baf-April inhibitor. I was exceptionally pleased with the rapidity and quality of the recently submitted BLA filing for POBI 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 POVI primary membranous nephropathy and the POVI 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 Kastjevi, I'm also very pleased with the rapidity and quality of this SBLA submission for Kastjevi in 5 to 11-year-olds with sickle cell disease or beta thalassemia. The Kastjevi 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, povine myasthenia gravis, and zamylocell 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 Olivtrek 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 Eliftrek 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 1 genotypes. As we expand the Oliftrec and Trikafta labels to additional mutations, we're also expanding the labels to younger patients. We will soon submit for approval for Oliftrec in patients 2 to 5 years of age, where you may recall our pivotal trial demonstrated a remarkable 65% of children reaching normal levels of CFTR function. and we also plan to submit for Trikafta in children 1 to 2 years of age in the near term. In addition, we continue to advance our next-generation 3.0 CFTR modulators, including VX828, which is currently in the 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 VX828 in the family of next-gen 3.0 are VX581 and VX272. both of which are currently in the clinic in Phase 1 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. And finally, on VX522, 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. and 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 VX522. 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, POVI and IGAN, POVI in primary membranous nephropathy, inoxiplin in AMKD, and VX407 in ADPKD. Tonight, I'll cover the first three programs, starting with POVI and IGAN. Recall, POVI's differentiated potential best-in-class profile stems from its specific design as an engineered tachyfusion protein with binding affinity, potency, and PK properties that deliver optimal dual BAFAPRIL 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 autoinjector. Overall, the Phase III interim analysis data represent a home run in terms of study design, execution, and the results, with POVI 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 SGLT2s seen in any IGAN study. Baseline characteristics were well matched to real-world IGAM patients in terms of age, renal function, and degree of pertinuria. 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 POVI group. To replay the top-line primary and secondary efficacy results, for the primary endpoint, POVI 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, POVI treatment led to a 77.4% reduction from baseline in serum GDIGA1 levels. That's a 79.3% reduction versus placebo. For the second secondary endpoint of those patients with hematuria at baseline, 85.1% of POVI-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 grams per gram, 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 POVI treatment. On safety, POVI was generally safe and well tolerated. The majority of adverse events were mild to moderate, and there were no serious adverse events related to POVI. 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 POVI groups. There were no opportunistic infections and no discontinuations related to POVI overall, including no discontinuations due to infections. Lastly, on anti-drug antibodies or ADAs, ADAs were observed as expected with biologics, but had no impact on POVI'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 POVI and primary membranous nephropathy, I am pleased to share we have completed enrollment of the Phase 2 portion of the Olympus Phase 2-3 study and have already initiated the Phase 3 portion ahead of our previously announced mid-2026 goal. And finally on POVI, 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 two proof of concept study of POVI in generalized myasthenia is underway. This is a 30 patient study of people with GMG evaluating both the 80 and 240 milligram 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 POVI 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 POVI'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 enoxaplin in APOL1-mediated kidney disease, or AMKD. First on amplitude, the pivotal phase 3 study of primary AMKD, that is to say patients with two APOL1 variants, pertinuric 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 IIb study of enaxiplin in separate populations. patients with 2-APOL1 variants, modest pertinuria, and no other kidney disease, and patients with 2-APOL1 variants, moderate to severe pertinuria, 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 confirmed 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 Zamylocell has very strong clinical results to date, as detailed in last year's 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-plus years of type 1 diabetes, undetectable endogenous insulin production at baseline, taking 40-plus 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 1-2-3 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.