Vertex Pharmaceuticals Incorporated

Good day and welcome to the Vertex Pharmaceuticals second quarter 2026 earnings call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist 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 1 on your touchtone phone. And to withdraw your question, please press star then 2. 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 second 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. Our pipeline, the proposed acquisition of Krenetics Pharmaceuticals and the expected benefits of that transaction, 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's second quarter performance was excellent, with strong momentum in the commercial portfolio, rapid progress across our R&D pipeline, and the announcement of the definitive agreement to acquire Krenetics Pharmaceuticals, which brings rare endocrine diseases as a fifth pillar to Vertex. Second quarter total revenue grew 12% year-on-year, driven by the strength of our cystic fibrosis portfolio and the growing contributions from our newer products, Caschevy and Jernavix. As I've previously highlighted, this is a year of execution for Vertex across commercial, clinical, and regulatory, and on each of those fronts, we advanced significantly in the second quarter. Commercially, we delivered strong revenue growth across all diseases, made meaningful progress in reimbursed access and continue to execute on near-term launch planning to drive the next phase of growth. Clinically, we continue to make significant progress in advancing our pipeline including completing enrollment in the Aglow Phase 2 study of VX407 in ADPKD, tracking to complete enrollment in the Amplitude Phase 3 study in AMKD by the end of this year, and reporting results from the interim analysis cohort of Amplitude in the beginning of 2027. We also remain on track to release results Later this year, from a proof of concept study in DM1 and an expanded population for AMKD in the amplified trial, as well as the initial patient data from VX828 in CF. On the regulatory front, the BLA for POVI and IGAN was accepted in the U.S. with a November 30th PDUFA date. We achieved expanded labeling in record time for Caschevy in patients ages 2 to 11 in the U.S., And I'm very pleased to share that as we continue to dose the Phase 1-2-3 study of Zamylocell in type 1 diabetes, the IND was cleared for the blood type O islet cells in our T1D program, VX017. We expect initiation of the VX017 Phase 1-2 study in the near term. Finally, with the announced acquisition of Krenetics Pharmaceuticals, we look forward to multiple benefits of the deal, establishing a fifth pillar in rare endocrine diseases, adding to our innovative R&D pipeline, accelerating revenue growth, and enhancing long-term earnings. Tonight, I'll limit my R&D comments to new news in CF, renal, and type 1 diabetes, and close with some additional remarks regarding the Krenetics acquisition. Thank you for joining us. Among children with CF under 12 years of age, the majority across all eligible genotypes achieve a sweat chloride less than 30 millimoles, which is the median among CF carriers. This is remarkable because at these sweat chloride levels, CF carriers do not exhibit the manifestations of disease. In addition, we have initiated global regulatory submissions for Lyftrac in children ages 2 to 5. Global regulatory submissions for Trikafta in patients ages 1 to 2 are also in progress. Turning to our next wave in CF and VX828, our next generation 3.0 CFTR modulator recently completed dosing in the patient cohort. and Data are expected in the second half of this year. Behind VX828, we continue to advance additional correctors in the NextGen 3.0 family, and both VX581 and VX272 are in healthy volunteer studies. Let me close on CF with this. Our ultimate goal has been consistent for two plus decades, to bring patients to carrier levels of sweat chloride. Frankly, a lift tracks remarkable results where nearly two-thirds of younger patients achieved sweat chloride levels less than 30 millimole per liter. and for patients ages 12 plus, more than 75% achieve sweat chloride levels within the carrier range of CFTR function means we are very close to that goal. Given the improvements in sweat chloride, PPFEV1, pulmonary exacerbations, hospitalizations, lung transplant, Thank you for watching. and cohorts of patients with CF. However, we will only advance assets into Phase 2 and beyond that show promise to beat a lift track. In other words, to bring even more patients to sweat chloride levels less than 30 across all genotypes with once daily dosing and excellent drug-like properties including drug-drug interactions. Anything less would not be competitive. Moving now to our renal franchise, where we have four programs in mid- and late-stage development, povitacicept in IGAN and primary membranous nephropathy, enaxiplin in APOL1-mediated kidney disease, NVX407 in ADPKD, or autosomal dominant polycystic kidney disease. Let me start with the most advanced program and significant milestone. In late May, the FDA accepted our BLA for POVI in IGAN and assigned a PDUFA date of November 30th of this year. As a reminder, the Rainier Phase III interim analysis was a home run, delivering statistically significant and clinically meaningful results across the primary and all secondary endpoints, with a favorable safety profile and consistency in the primary endpoint of change from baseline We are in the final stages of launch readiness. Duncan will provide more details regarding our approach and excitement to go to market with POVI's differentiated profile of potentially best-in-class efficacy, a well-tolerated safety profile, and patient-centric administration through small-volume, once-monthly dosing via an auto-injector at home. We are also advancing POVI internationally. We have completed the regulatory submission for accelerated approval of POVI in IGAN in Saudi Arabia, where POVI has received breakthrough designation. Turning to POVI in membranous nephropathy, our Olympus Phase 2-3 pivotal trial is well underway. The Phase 2 portion is complete, and the Phase 3 portion initiated last quarter. I'm pleased to share that the IDMC has completed its review and selected the Phase 3 dose, 80 mg subcutaneously, every four weeks. We hold fast-track, orphan drug designation, and EMA prime designations for POVI in membranous. Stepping briefly outside of renal, on POVI in Myasthenia Gravis, I'm also pleased to share that the 30-patient Phase 2 Proof of Concept Study is on track to complete enrollment by the end of this year. Recall, this study evaluates 80 mg and 240 mg doses of POVI versus placebo for 12 weeks. Turning now to Anaxipline in AMKD. On Amplitude, our pivotal Phase 2-3 study in AMKD, we completed enrollment of the Interim Analysis cohort in September of last year and are on track to complete full enrollment by the end of this year. The interim analysis will be conducted following 48 weeks of treatment and we remain on track to share these IA results in early 2027. If positive, we would be positioned to file for potential accelerated approval in the US thereafter. Amplified is our Phase IIb basket study of enaxiplin in AMKD patients with either lower proteinuria or AMKD patients with diabetes. Expanded patient populations not studied in amplitude. The Amplified study has completed enrollment and dosing, and we expect to share results this fall. Lastly in the renal portfolio is VX407 in ADPKD or autosomal dominant polycystic kidney disease. Our Aglow Phase 2 study has completed enrollment. This is a proof-of-concept study with up to 52 weeks of treatment. We are excited about the potential for VX407 in ADPKD and look forward to sharing more information as dosing continues and the data matures. Let me now touch on type 1 diabetes. We had very constructive meetings with the FDA following our voluntary pause in order to conduct a manufacturing analysis of a Zamylocell. As we shared on our Q1 call, we have resumed dosing patients in the Zamylocell Phase 1-2-3 study. Thank you for watching. By designing and bringing to market VX017, another allogeneic, off-the-shelf, glucose-responsive, insulin-producing, fully differentiated islet cell therapy, in this case for any blood type, we anticipate doubling our market opportunity from about 60,000 to about 120,000 patients. A silver lining to the pause we took in the Zamyla Cell Type A program is that the Type O program time differential versus Zamyla Cell has shortened. Type O is making rapid progress, and thus we are considering options to further streamline our regulatory strategy and commercialization approach. We expect to provide updated T1D plans, including timelines, later this year. Thank you so much for joining us. Thank you for watching. We believe the two lead assets, Palsonify and Achumelnant, together represent a peak sales opportunity of about $5 billion. Both are small molecules that address serious diseases for patients, treated by a concentrated group of specialized endocrinologists. This fits directly within Vertex's proven, efficient, specialty commercial model. We enter this transaction from a position of strength. We view CF as a long-duration franchise with sustained growth. We continue to expect both Caschevy and Gernavix to be multi-billion dollar assets, and we anticipate our emerging renal franchise could one day rival CF in revenue. In addition, we have a broad and deep pipeline in earlier stages of development. The Krenetics acquisition will add to this innovation pipeline, Thank you for watching.