Vertex Pharmaceuticals Incorporated

Good day and welcome to the Vertex Pharmaceuticals first quarter 2025 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. To ask a question, you may press star then one on your touchtone phone. And to withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Ms. Suzy Lisa. Please go ahead, ma'am.

Good evening, all. My name is Suzy Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our first quarter 2025 Financial Results Conference Call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Stuart Arbuckle, Chief Operating Officer, Charlie Wagner, Chief Financial Officer, and Duncan McKechnie, SVP, North America Commercial Operations, and come July 1, 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, are pipelined 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 will now turn the call over to Reshma.

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Continuing the momentum from 2024, we've kicked off 25 with another quarter of strong performance across the board, growing and diversifying revenue as we execute on multiple launches, accelerating programs in pivotal development, and advancing the R&D pipeline. We continue to reach more patients with more products and delivered 2.77 billion in revenue in the first quarter, representing 3% growth versus Q1, 2024. This year, we are keenly focused on commercialization and we are pleased with the early launch dynamics and physician and patient feedback on Olivtrec, our fifth CF medicine, and Jurnavix, the first oral non-opioid for moderate to severe acute pain in more than two decades, both of which were approved in the U.S. in just the last few months. With these approvals and the continued global launch of Casgevi, our gene-edited therapy for sickle cell disease and beta-thalassemia, we are significantly expanding the number of patients we serve. We are also sharply focused on advancing the four programs currently in pivotal development. Sucetragine in diabetic peripheral neuropathy, Zamylocell in type 1 diabetes, Enaxiplin in APOL1-mediated kidney disease, and POVI in IgA nephropathy. Importantly, three of these phase three programs are on track to complete enrollment of the interim analysis cohort or the full study this year, setting up a series of potential filings in 2026. And as we approach the one-year anniversary of the acquisition of Alpine Immune Sciences, I wanted to highlight two big recent povitacicep-related milestones. First, we completed enrollment in the interim analysis cohort in the Phase III Rainier IGAN trial. And second, we reached agreement with the FDA to advance POVI to pivotal development in a second indication, primary membranous nephropathy. This is a notable milestone as POVI continues to deliver on its promise as a pipeline and a product with best-in-class potential. The start of the POVI membranous study will also mark our fifth program in pivotal development. Tonight, I'll limit my R&D comments on the pipeline programs with the most significant new information to share, specifically CF, pain, type 1 diabetes, and the kidney programs, starting with CF. Following our December U.S. approval of a lift track, we have gained MHRA approval in the U.K. and a positive CHMP opinion in the E.U. As a result, we expect potential approval from the European Commission for a lift track in the second half of this year, along with potential approvals in Canada, Australia and Switzerland. These approvals are in addition to the European Commission's early April approval of CAF TRIO for rare mutations, which followed similar approvals for Trikafta rare mutations in the U.S. and Canada late last year, adding hundreds of additional eligible patients in North America and thousands in Europe. These approvals are a direct result of the team's decades-long, painstaking work to establish and verify the hypothesis that the three unique binding sites of our CFTR modulators results in overall protein stabilization and have the potential to transform the lives of nearly 95% of patients with CF. Stuart will share more on the U.S. Electrek launch shortly. Next on the horizon for our CF small molecule program is the NextGen or NG3.0 CFTR regimen. With this program, we seek to reach our longstanding goal of bringing most, if not all, patients with CF to normal levels of CFTR function. The backbone of this NG3.0 combination is VX828, the most efficacious CFTR corrector that we have ever studied in vitro. It is completing Phase 1 development and we remain on track to initiate a study with VX828 in patients with CF before the end of this year. For the ongoing Phase 1-2 study of VX522 for the approximately 5,000 or so patients, who cannot benefit from our CFTR modulators, we have recently implemented a temporary pause to the study as we assess a tolerability issue. Given that this remains an active clinical trial, we won't be providing any additional details at this time so as to maintain study integrity. We will update you when we know more. Moving next to the pain programs. First, the Phase III study of sucetragine in diabetic peripheral neuropathy, a chronic peripheral neuropathic pain condition that affects over 2 million Americans annually, is well underway with ongoing enrollment and dosing. As a reminder, sucetragine has fast-track designation for peripheral neuropathic pain and breakthrough designation for diabetic peripheral neuropathy. Next, I'm very pleased to share that the study of oral VX993, another NAV1.8 inhibitor, in acute pain post-bunionectomy is on track to complete this quarter, and we expect to report results from this trial in the second half of this year. VX993 has fast-track designation for acute pain in both the oral and IV formulations. Lastly, we continue to make solid progress with additional NAV1.8 inhibitors beyond VX993, as well as in our NAV1.7 pain signal inhibitor program that may be used alone or in combination with NAV1.8 inhibitors. Transitioning now to type 1 diabetes. Zamyla Cell remains on track to complete enrollment and dosing of its pivotal study this quarter, positioning us for global regulatory submissions in 2026, if the data are supportive. Recall, we expect about 60,000 severe type 1 diabetics who may potentially benefit from this first Zamyla Cell submission. Based on the high unmet need in T1D and the transformative nature of this therapy, Zamyla Cell has multiple global regulatory designations, including RMAT and FastTrack in the US, Prime in the EU, and the Innovation Passport in the UK. In our other T1D work, following the recent data from VX264 or the Cells Plus Device Program, we have returned this approach to the research stage. We continue to make preclinical progress on our other approaches to cloak the VX880 cells from the immune system. These cells have already demonstrated transformative efficacy. These approaches include alternative immunosuppressive regimens and gene editing to make hypoimmune islet cells. And we look forward to updating you as these programs advance. Finally, a few updates on our kidney portfolio, which now has clinical stage programs in four renal diseases, IgA nephropathy, AMKD, membranous nephropathy, and ADPKD, or autosomal dominant polycystic kidney disease. Starting with povitacicept, a potential best-in-class dual antagonist of the BAF and APRIL cytokines, which play a key role in the pathogenesis of B-cell-mediated autoimmune diseases. First, in IGAN, as mentioned earlier, I am very pleased to share that we have completed enrollment in the interim analysis cohort of the Rainier Phase III trial. Once this cohort completes 36 weeks of treatment, we will conduct the interim analysis, and if positive, it will support filing in the first half of 2026 for potential accelerated approval in the U.S. In addition, our program to support the launch of POVI with a subcutaneous auto-injector for monthly at-home administration is well underway. And for full approval, we are making strong progress towards our goal of enrolling the complete cohort of 480 patients, in whom we will assess eGFR through week 104. Second, based on the positive results from the Ruby 3 basket study, we have reached agreement with the FDA to advance POVI to pivotal development in membranous nephropathy. Beginning in the second half of this year, we are planning to initiate a single Phase 2-3 adaptive study of POVI versus standard of care with the primary endpoint of complete remission at week 72. Next, two highlights on enaxiplin for APOL1-mediated kidney disease, or AMKD. First, we remain on track to complete enrollment in the interim analysis cohort of the AMPLITUDE pivotal trial this year. AMPLITUDE is a study of primary AMKD, that is to say, patients with two ApoL1 variants and no additional renal-related comorbidities. After completing enrollment, when this cohort reaches 48 weeks of treatment, we will conduct an interim analysis. If positive, we will be poised to file for potential accelerated approval in the U.S. Second, based on the positive proof-of-concept results of inoxiplin in primary AMKD, the momentum in the Phase III study, and interest from the community, we recently initiated the amplified study. Amplified is a Phase II proof-of-concept study of enoxiplin in patients with AMKD and other comorbidities, including type 2 diabetes. This study is enrolling and dosing patients. To close on our kidney pipeline, a few comments on VX407 in autosomal dominant polycystic kidney disease or ADPKD. VX407 is a first-in-class small molecule protein folding corrector that is designed to target the underlying cause of ADPKD by restoring PC1 protein function, thereby reducing total kidney volume and preventing progression to kidney failure. As a reminder, by way of its mechanism of action, VX407 addresses up to 10% of ADPKD patients. And, as in CF, we will seek to expand the eligible patient population with serial innovation over time. We have completed the Phase 1 trial of VX407 and the PK and safety are supportive of advancement. The Phase 2 proof-of-concept study is designed as a 52-week, single-arm study of 24 patients that will evaluate the efficacy of VX407 as measured by the height-adjusted total kidney volume, and we are on track to initiate this study in the second half of this year. For five years now, at the end of my remarks, I've turned the call over to Stuart. I'll do so for the final time tonight. Let me acknowledge and thank Stuart once again for the incredible run at Vertex and wish him the very best in retirement. With that, I'll now turn the call over to Stuart and Duncan for a commercial update.