Alpine Immune Sciences, Inc.

Good day and welcome to the Vertex Pharmaceuticals first quarter 2024 earnings conference 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. 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 2024 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, and Charlie Wagner, Chief Financial 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, and beta thalassemia, our pipeline, Vertex's anticipated acquisition of Alpine Immune Sciences, 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. In addition, the impact of foreign exchange is presented inclusive of our foreign exchange risk management program. 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 our strong momentum from 2023, we've kicked off 24 with another quarter of excellent performance across the board. Vertex continued to reach more CF patients, delivering $2.7 billion in revenue in Q1, representing 13% growth versus the prior year period. We also began our journey of revenue diversification with the launch of Caschevy in both sickle cell disease and beta thalassemia in multiple regions. In our late stage pipeline, we continue to drive programs into phase three and towards regulatory approval, creating multiple opportunities for both revenue growth and diversification, including, one, completing our regulatory submissions for the vanzecaptor triple in patients with cystic fibrosis six years and older in both the U.S. and the EU, initiating the rolling NDA submission for VX548 or susceptrogene in moderate to severe acute pain. Three, advancing enaxiplin into the phase three portion of its pivotal trial in APOL1-mediated kidney disease and expanding the eligible patient population down to age 10. And four, following the successful completion of the end of phase two regulatory meeting with the FDA, we are on track to initiate the phase three trials of sucetragine in painful diabetic peripheral neuropathy in the second half of this year. And milestones in our early and mid-stage pipeline matched this pace of progress as we resumed the VX880 trial in type 1 diabetes, initiated clinical development of VX407 in polycystic kidney disease, and three, achieved regulatory clearances in multiple regions, including the U.S., and initiated the phase 1-2 clinical trial of VX670 in patients with myotonic dystrophy type 1. And, of course, we are very excited to expand the Vertex portfolio and team with our definitive agreement to acquire Alpine Immune Sciences, announced on April 10th. Alpine's lead asset, povitacicept, or POVI, is a potential best-in-class, Phase III-ready molecule for IgA nephropathy, or IGAN, a disease with high unmet need. POVI is also a molecule that holds a pipeline in a product potential in a number of other serious autoimmune renal diseases and cytopenias in phase two development. We see the acquisition as just the right fit with just the right assets at just the right phase of development where Vertex's capabilities can accelerate POVI's development in IGAN and other indications. And lastly, Alpine will add protein engineering and immunotherapy expertise to Vertex's capabilities with particular relevance for our development programs in gentler conditioning for Casgevi and immune evasion for our type 1 diabetes cell therapies. We are excited to begin working with the Alpine team and together advance POVI into phase 3 in IGAN later this year. With that overview, let me now turn to a more detailed pipeline review. This quarter, I'll limit my comments to the programs with the most significant recent updates, cystic fibrosis, pain, type 1 diabetes, and the pending alpine acquisition. starting with CF. We are very pleased with the phase three results of the Vanser triple we announced in early February, as we continue to advance towards our ultimate goal of bringing all eligible patients to carrier levels of sweat chloride. results from the vanza pivotal program met our high expectations and were an important milestone in our progress towards this aspiration results from the two randomized studies in patients 12 and above demonstrated vanza was non-inferior to tricafta on lung function and superior to Trikafta on sweat chloride, including as measured by the proportion of patients achieving sweat chloride levels below the diagnostic threshold of 60 millimoles per liter and below the carrier level or normal levels of sweat chloride of less than 30 millimoles per liter. Included in the pivotal program was the Ridgeline study in patients 6 to 11 years of age. To underscore the potential impact of vanzecaftor, consider 95% of patients age 6 to 11 in this study achieved sweat chloride levels below the level of diagnosis for cystic fibrosis. and more than half reached sweat chloride levels considered to be in the normal or carrier level range of sweat chloride. We believe these results indicate that VANSA could set a new standard in the treatment of CF. To round out the profile of the vancicaftor triple, it's important to note that the therapy also offers the convenience of once daily dosing and a substantially lower royalty burden. With these results in hand, we've been working rapidly to compile the regulatory marketing applications. And I'm pleased to share that we have completed submissions in the US and EU for patients ages six years and older ahead of our mid-year goal. In the U.S., we use one of our priority review vouchers, which, if the filing is accepted, provides an expedited six-month review versus the standard 10-month review timeline. We're also on track to complete submissions in the U.K., Canada, Australia, New Zealand, and Switzerland by mid-year. I'll close on CF with VX522, our CFTR mRNA therapy in development with our partners at Moderna for the treatment of the more than 5,000 people with CF who do not make any CFTR protein and therefore cannot benefit from CFTR modulators. We continue to enroll in the multiple ascending dose portion of the study and expect data late in 2024 or early 2025. Moving to the pain program and sucetragine, our novel, highly selective NAV1.8 pain signal inhibitor. Sucetragine offers the compelling combination of both strong safety and strong efficacy, with the potential to treat moderate to severe pain across multiple settings of care. In acute pain, SysetraGene has secured fast-track and breakthrough therapy designations, and we were very pleased that the FDA granted us a rolling NDA submission. I'm also pleased to share that multiple modules have already been submitted, and we are on track to complete the submission this quarter. Consistent with our serial innovation strategy, the next asset in our acute pain pipeline is VX993. We recently received IND clearance for the intravenous formulation of VX993 and have already started the phase 1 trial. We're also planning a VX993 oral formulation phase 2 study in acute pain, which we expect to initiate later this year. Beyond sesetragine and VX993, we continue to innovate in the NAV1.8 space and are also making strong progress preclinically with our NAV1.7 pain signal inhibition program that may be used alone or in combination with sesetragine or other NAV1.8 inhibitors. In peripheral neuropathic pain, or PNP, we are very pleased with the outcomes from the recently completed end-of-Phase II meeting with the FDA and are excited to begin the pivotal program for sucetragine in painful diabetic peripheral neuropathy, or DPN, in the second half of this year. The program will consist of two randomized sister studies of approximately 1,000 patients each with three arms in each study. A sucetragine 70 milligram arm once daily, a placebo arm, and a pregabalin or Lyrica arm. The efficacy endpoints are based on the change from baseline to week 12. The primary endpoint is the comparison of sucetragine versus placebo in the weekly average of the daily pain intensity score, or NPRS. The first key secondary endpoint will test for non-inferiority of sucetragine to pregabalin on the same NPRS pain score, and if successful, we will test for superiority. And finally, the second key secondary is quality of life measures versus placebo. In order to evaluate the long-term safety and effectiveness of sucetragine, a subset of patients completing the 12-week study will have the opportunity to roll into a 52-week open-label extension study. Our goal continues to be a broad peripheral neuropathic pain label, and in support of this goal, we're also studying sucetragine in lumbosacral radiculopathy, or LSR. a PNP condition for which there are no specifically indicated or approved treatments. LSR accounts for approximately 40% of all PNP patients and together with DPN make up more than 60% of the PNP segment. We are continuing to enroll and dose our Phase II study of sucetragine in LSR, and I am pleased to share that the study is on track to complete enrollment by the end of this year. Just as we transformed the treatment of CF, we believe we have the potential to transform the treatment of pain, both acute and neuropathic, and look forward to helping address the unmet need of the tens of millions of Americans suffering with these conditions. Turning now to type 1 diabetes. VX880 is a stem cell-derived, fully differentiated islet cell therapy for patients with T1D and impaired hypoglycemic awareness who suffer from severe hypoglycemic events. I'm pleased to share that after data review by the Independent Data Monitoring Committee, the VX880 study has resumed. Parts A, B, and C of the global 17-patient study are fully enrolled, and we expect to complete dosing soon. We look forward to sharing updated data this June at the American Diabetes Association annual meeting. VX264, the next asset in our T1D program, is our cells plus device program. Using the same VX880 cells, which have already demonstrated efficacy, VX264 is designed to eliminate the need for immunosuppression by shielding the cells from the immune system in the proprietary device. This Phase 1-2 study has completed Part A, and Part B is underway. Lastly, our hypoimmune program, which aims to evade the immune system by introducing certain edits into the same VX880 cells, is yet another approach to avoiding the use of immunosuppressives. This program continues to advance in preclinical development. I'll conclude with a few comments on povitacicept, the lead asset from our pending acquisition of Alpine Immune Sciences. We are excited about the potential of povitacicept across multiple dimensions, including preclinically with its high affinity and potency against both APRIL and BAF pathways in preclinical assays, as well as high efficacy in cell and animal models of B-cell driven diseases. clinically with patient data in IGAN through Phase II that look potentially best in class in proteinuria, in hematuria, GFR, and clinical remission. Better drug-like properties with direct patient benefit, including once every four-week dosing, subcutaneously with low injection volume. A good safety and tolerability profile. The broadest development plan in the field. And a robust IP portfolio. Important upcoming POVI milestones in the second half of this year include initiation of the Phase 3 study in IGAN and readouts from the ongoing Ruby 3 and Ruby 4 basket studies in autoimmune renal diseases and cytopenias, respectively. With that, I'll turn it over to Stuart for a commercial overview.