Tezacaftor

BOSTON--( BUSINESS WIRE )--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today reported consolidated financial results for the third quarter ended September 30, 2024, and raised its full-year product revenue guidance to $10.8 billion to $10.9 billion. “ The third quarter marked another period of strong progress, with continued revenue growth and outstanding execution across the business, and we are again increasing our full-year product revenue guidance,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “ Launch preparedness is well underway as we look forward to the potential approvals of the vanzacaftor triple for cystic fibrosis and suzetrigine, a new class of medicine for moderate-to-severe acute pain. With a broad and deep pipeline and three additional programs advancing to Phase 3 development in the last quarter alone, Vertex is well positioned for continued long-term growth.” Third Quarter 2024 Results Product revenue increased 12% to $2.77 billion compared to the third quarter of 2023, primarily driven by the continued strong performance of TRIKAFTA ® /KAFTRIO ® . Net product revenue in the third quarter of 2024 increased 10% to $1.71 billion in the U.S. and increased 14% to $1.06 billion outside the U.S., compared to the third quarter of 2023. Combined GAAP and Non-GAAP R&D and SG&A expenses were $1.2 billion and $1.1 billion, respectively, compared to $1.1 billion and $942 million, respectively, in the third quarter of 2023. The increases were due to increased commercial investment to support launches of Vertex's therapies globally and continued investment in support of additional programs that have advanced to Phase 3 clinical development. Acquired IPR&D (AIPR&D) expenses were $15 million compared to $52 million in the third quarter of 2023. GAAP effective tax rate was 14.6% compared to 12.2% for the third quarter of 2023. Both periods included R&D tax credits for the current and prior years and excess tax benefits related to stock-based compensation. Non-GAAP effective tax rate was 19.8% compared to 19.4% for the third quarter of 2023. Please refer to Note 1 for further details on Vertex’s GAAP to Non-GAAP tax adjustments. GAAP and Non-GAAP net income were $1.0 billion and $1.1 billion, respectively, for each of the third quarters of 2024 and 2023. Increased product revenue was partially offset by increased R&D and SG&A expenses compared to the third quarter of 2023. Cash, cash equivalents and total marketable securities as of September 30, 2024 were $11.2 billion, compared to $13.7 billion as of December 31, 2023. The reduction in Vertex’s cash, cash equivalents and marketable securities balance compared to December 31, 2023, was due to the cash consideration paid to acquire Alpine Immune Sciences in the second quarter of 2024 and repurchases of our common stock pursuant to our share repurchase program, partially offset by positive cash flows provided by other operating activities. Full-Year 2024 Financial Guidance Vertex today raised its full-year 2024 product revenue guidance from $10.65 billion to $10.85 billion to $10.8 billion to $10.9 billion. Vertex’s product revenue guidance includes expectations for continued growth in CF as well as for the launch of CASGEVY in approved indications and geographies. Given the impact of the Alpine acquisition, for 2024, Vertex is providing guidance for both combined GAAP and Non-GAAP R&D and SG&A expenses and for AIPR&D expenses. Vertex continues to expect combined Non-GAAP R&D and SG&A expenses to be in a range of $4.2 billion to $4.3 billion for the full year. This includes Vertex’s expectations for continued investment in multiple mid- and late-stage clinical development programs and commercial and manufacturing capabilities. Vertex also continues to expect 2024 AIPR&D expenses of approximately $4.6 billion for the full year, including the Alpine acquisition-related charge of $4.4 billion in the second quarter of 2024. Vertex’s updated financial guidance is summarized below: Current FY 2024 Previous FY 2024 Total product revenue $10.8 to $10.9 billion $10.65 to $10.85 billion Combined GAAP R&D and SG&A expenses (2) Unchanged $5.0 to $5.2 billion Combined Non-GAAP R&D and SG&A expenses (2) Unchanged $4.2 to $4.3 billion AIPR&D expenses Unchanged $4.6 billion* Non-GAAP effective tax rate** ~90% ~100% *Includes Alpine AIPR&D expense of $4.4 billion. **Vertex’s full-year Non-GAAP tax rate is impacted by the Alpine AIPR&D expense, which is non-deductible for tax. Key Business Highlights Marketed Products and Potential Near-Term Launch Opportunities Cystic Fibrosis (CF) Portfolio Vertex anticipates the number of CF patients taking its medicines will continue to grow through new approvals and reimbursement for the treatment of younger patients. Recent and anticipated progress includes: As of the third quarter of 2024, KAFTRIO is now reimbursed in all 27 countries of the European Union. The U.S. Food and Drug Administration (FDA) has assigned the once-daily vanzacaftor triple in people with CF 6 years and older a Prescription Drug User Fee Act (PDUFA) target action date of January 2, 2025. The vanzacaftor triple was granted Priority Review by the FDA. Vertex has completed regulatory submissions for the vanzacaftor triple in the European Union (EU), the United Kingdom (U.K.), Canada, Australia, New Zealand and Switzerland, and reviews are underway. In July, Health Canada granted approval to TRIKAFTA for an additional 152 rare mutations in the CFTR gene. Vertex has submitted regulatory applications to the FDA and the European Medicines Agency (EMA) for TRIKAFTA/KAFTRIO for the treatment of people with CF and rare responsive mutations. CASGEVY for the treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) CASGEVY ® is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT that has been shown to reduce or eliminate vaso-occlusive crises (VOCs) for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved in the U.S., Great Britain, the EU, the Kingdom of Saudi Arabia (KSA), the Kingdom of Bahrain (Bahrain), Canada and Switzerland for the treatment of both SCD and TDT, and launches are ongoing. Vertex received regulatory approvals for CASGEVY for the treatment of patients 12 years of age and older with SCD or TDT in Switzerland and Canada. As of mid-October, Vertex has activated 45 authorized treatment centers (ATCs) globally and increasing numbers of patients across all regions have initiated cell collection. In the third quarter of 2024, Vertex’s product revenue included revenue from the first patient infused with CASGEVY. Vertex announced a reimbursement agreement with NHS England for eligible patients with TDT to access CASGEVY. Vertex has also entered into commercial discussions with NHS England to secure access to CASGEVY for eligible patients with SCD. The Italian Medicines Agency approved Vertex’s request for the implementation of an early access program (EAP), for the use of CASGEVY for the treatment of TDT and SCD. Suzetrigine (VX-548) for the treatment of moderate-to-severe acute pain Vertex has discovered and continues to advance multiple selective small molecule inhibitors of NaV1.8, with the goal of creating a new class of pain medicines that has the potential to provide effective pain relief without the limitations of opioids and other currently available medicines. The FDA has assigned a PDUFA target action date of January 30, 2025, for suzetrigine for the treatment of moderate-to-severe acute pain. Suzetrigine was granted Priority Review by the FDA. Select Clinical-Stage R&D Pipeline Cystic Fibrosis Vertex continues to pursue next-in-class, small molecule, oral CFTR modulators for the ~90% of people with CF who may benefit from such an approach, as well as a nebulized mRNA therapy for the more than 5,000 people with CF who do not make CFTR protein and cannot benefit from CFTR modulators. Vanzacaftor/tezacaftor/deutivacaftor, the once-daily, next-in-class triple oral small molecule combination, in cystic fibrosis Vertex is enrolling and dosing a study in children with cystic fibrosis ages 2 to 5 years who have at least one F508del mutation or a mutation responsive to triple combination CFTR modulators. Consistent with its commitment to serial innovation and bringing as many patients as possible to normal levels of CFTR function, Vertex continues to advance new oral small molecule combination therapies through preclinical and clinical development. The most advanced next-wave CFTR modulators have completed, or are in the process of completing, Phase 1 clinical trials. VX-522, nebulized mRNA therapy Vertex completed the single ascending dose (SAD) portion of the Phase 1/2 study of VX-522 in people with CF in late 2023, and the multiple ascending dose (MAD) portion of the study is ongoing. Vertex expects to complete the trial and share data in the first half of 2025. Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia Vertex has completed enrollment in two global Phase 3 studies of CASGEVY in children 5 to 11 years of age with SCD or TDT and the trials are ongoing. Vertex continues to work on preclinical assets for gentler conditioning for CASGEVY, which could broaden the eligible patient population. Acute Pain Vertex has initiated a Phase 2 study for an oral formulation of VX-993, a next-generation selective NaV1.8 pain signal inhibitor, for the treatment of moderate-to-severe acute pain following bunionectomy surgery. Vertex continues to enroll and dose the Phase 1 trial for an intravenous formulation of VX-993. The FDA has granted Fast Track Designation to VX-993 in moderate-to-severe acute pain in both its oral and intravenous formulations. Peripheral Neuropathic Pain (PNP) Vertex has initiated the Phase 3 pivotal program of suzetrigine in patients with painful diabetic peripheral neuropathy (DPN), a type of PNP that accounts for approximately 20% of patients suffering from PNP. The FDA has granted suzetrigine Breakthrough Therapy Designation in DPN. Vertex has completed the Phase 2 study of suzetrigine in painful lumbosacral radiculopathy (LSR), a condition representing more than 40% of patients suffering from PNP. Vertex continues to expect to share results from this study by the end of the year. Vertex has also initiated a Phase 2 study for the oral formulation of VX-993 for the treatment of DPN. Consistent with its commitment to serial innovation and leadership in pain, Vertex continues to develop additional NaV1.8 inhibitors and NaV1.7 inhibitors, for stand-alone use or in combination, for the treatment of acute and peripheral neuropathic pain. APOL1-Mediated Kidney Disease (AMKD) Vertex has discovered and advanced multiple oral, small molecule inhibitors of APOL1 function, pioneering a new class of medicines that targets the underlying genetic driver of this kidney disease. Vertex continues to enroll and dose patients with AMKD in the Phase 3 portion of the global Phase 2/3 pivotal clinical trial of inaxaplin, in which a 45 mg once-daily dose of inaxaplin is compared to placebo, on top of standard of care. IgA Nephropathy (IgAN) and Other B Cell-Mediated Diseases Vertex is developing povetacicept, a dual inhibitor of the BAFF and APRIL pathways, as a potentially best-in-class approach to treat immunoglobulin A (IgA) nephropathy. Vertex is also studying povetacicept in other serious B cell-mediated diseases, including autoimmune kidney diseases, such as primary membranous nephropathy, and autoimmune cytopenias. Vertex has initiated the RAINIER study, the Phase 3 clinical trial of povetacicept in IgA nephropathy. RAINIER is a global pivotal trial of povetacicept 80 mg vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating the change from baseline in urine protein creatinine ratio (UPCR) for the povetacicept arm versus placebo after a certain number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total estimated glomerular filtration rate (eGFR) slope through Week 104. Vertex presented updated data on 54 patients with IgAN from the RUBY-3 Phase 1b/2 basket study of povetacicept at the American Society of Nephrology (ASN) Annual Meeting. Treatment with povetacicept 80 mg dosed subcutaneously every four weeks demonstrated a clinically meaningful decrease in proteinuria, with a mean 66% reduction from baseline in UPCR (n=8) at 48 weeks associated with stable renal function over 48 weeks as assessed by eGFR. By 48 weeks, 63% (5 out of 8) of study participants achieved clinical remission, defined as UPCR < 0.5 g/g, negative hematuria, and stable renal function (≤ 25% reduction in eGFR from baseline). Treatment with povetacicept 240 mg dosed subcutaneously every four weeks was associated with similar improvements in proteinuria, and stable renal function, and both doses have been well tolerated in patients with IgAN. Vertex also presented emerging data on povetacicept from RUBY-3 in patients with primary membranous nephropathy (pMN) at ASN. Treatment with povetacicept 80 mg dosed subcutaneously every four weeks demonstrated a mean 62% reduction from baseline in UPCR (n=3) at 24 weeks, associated with stable renal function. By week 24, 2/3 of patients (67%) had achieved partial clinical remission, defined as UPCR < 3.5 g/g and ≥50% reduction in UPCR from baseline. Povetacicept was also well-tolerated in these patients with pMN. Vertex is studying additional renal diseases in the RUBY-3 basket study and hematologic conditions in the RUBY-4 basket study, both of which are ongoing. Type 1 Diabetes (T1D) Vertex is evaluating stem cell-derived, fully differentiated islet cell therapies for patients suffering from T1D, with the goal of developing a potential one-time functional cure for this disease. VX-880, fully differentiated islet cells with standard immunosuppression: Following successful end of Phase 2 meetings with the FDA, EMA and the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), Vertex has reached agreement to advance VX-880 into pivotal development with the conversion of the ongoing Phase 1/2 study to a Phase 1/2/3 study. The Phase 1/2/3 study will include a total of 50 patients infused with a single, target dose of VX-880. The primary endpoint is the proportion of patients with insulin independence and absence of severe hypoglycemic episodes (SHEs). VX-264, fully differentiated islet cells encapsulated in an immunoprotective device: The clinical trial for VX-264, which encapsulates the same VX-880 islet cells in a novel device so that treatment with immunosuppressants is not required, is a global, multi-part, Phase 1/2 study. Vertex has completed Part A of the study. As with the VX-880 study, patients in Part A receive a low dose with a stagger period between dosing. Part B of the Phase 1/2 study is enrolling and dosing patients. In Part B, patients receive the full target dose with a stagger period between patients, and in Part C, patients will receive the full target dose with no stagger. Vertex expects to share initial data from this study in 2025. Hypoimmune, edited fully differentiated islet cells: Vertex’s hypoimmune cell program involves editing the same stem cell-derived, fully differentiated VX-880 islet cells to protect the cells from the immune system, hence avoiding the need for immunosuppression. This research-stage program continues to make progress. Myotonic Dystrophy Type 1 (DM1) Vertex is evaluating multiple approaches that target the underlying cause of DM1, the most prevalent muscular dystrophy in adults, with ~110,000 people living with the disease in the U.S. and Europe and no approved therapies. Vertex’s lead approach, VX-670, in-licensed from Entrada Therapeutics, is an oligonucleotide linked to a cyclic peptide to promote effective delivery into the cell and its nucleus and holds the potential to address the underlying cause of DM1. Vertex recently completed the single ascending dose (SAD) portion of the global Phase 1/2 clinical trial for VX-670 in people with DM1. Vertex has initiated the MAD portion of the Phase 1/2 study, in which both the safety and efficacy of VX-670 will be evaluated. Autosomal Dominant Polycystic Kidney Disease (ADPKD) Vertex is developing small molecule correctors that restore function to the variant polycystin 1 (PC1) protein, with the goal of addressing the underlying cause of ADPKD, the most common genetic kidney disease, affecting approximately 250,000 people in the U.S. and Europe. Vertex continues to enroll and dose its Phase 1 clinical trial in healthy volunteers for VX-407, a first-in-class small molecule corrector that targets the underlying cause of ADPKD in patients with a subset of variants in the PKD1 gene, which encodes the PC1 protein, estimated to be ~25,000 (or ~10%) of the overall patient population. Non-GAAP Financial Measures In this press release, Vertex's financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results and guidance exclude from Vertex's pre-tax income (loss) (i) stock-based compensation expense, (ii) intangible asset amortization expense, (iii) gains or losses related to the fair value of the company's strategic investments, (iv) increases or decreases in the fair value of contingent consideration, (v) acquisition-related costs, and (vi) other adjustments. The company's non-GAAP financial results also exclude from its provision for income taxes the estimated tax impact related to its non-GAAP adjustments to pre-tax income (loss) described above and certain discrete items. These results should not be viewed as a substitute for the company’s GAAP results and are provided as a complement to results provided in accordance with GAAP. Management believes these non-GAAP financial measures help indicate underlying trends in the company's business, are important in comparing current results with prior period results and provide additional information regarding the company's financial position that the company believes is helpful to an understanding of its ongoing business. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, to manage the company's business and to evaluate its performance. The company’s calculation of non-GAAP financial measures likely differs from the calculations used by other companies. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the attached financial information. The company provides guidance regarding combined R&D and SG&A expenses and effective tax rate on a non-GAAP basis. The guidance regarding Acquired IPR&D expenses does not include estimates associated with any potential future business development transactions, including collaborations, asset acquisitions and/or licensing of third-party intellectual property rights. The company does not provide guidance regarding its GAAP effective tax rate because it is unable to forecast with reasonable certainty the impact of excess tax benefits related to stock-based compensation and the possibility of certain discrete items, which could be material. Vertex Pharmaceuticals Incorporated Consolidated Statements of Income (in millions, except per share amounts)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Product revenues, net $ 2,771.9 $ 2,483.5 $ 8,108.1 $ 7,351.5 Costs and expenses: Cost of sales 392.6 318.7 1,107.1 894.2 Research and development expenses 875.9 810.0 2,631.6 2,338.3 Acquired in-process research and development expenses 15.0 51.7 4,540.9 509.3 Selling, general and administrative expenses 371.8 263.8 1,086.7 767.5 Change in fair value of contingent consideration 0.3 1.2 0.7 (1.3 ) Total costs and expenses 1,655.6 1,445.4 9,367.0 4,508.0 Income (loss) from operations 1,116.3 1,038.1 (1,258.9 ) 2,843.5 Interest income 132.2 167.9 469.9 435.2 Interest expense (7.5 ) (10.9 ) (27.8 ) (33.5 ) Other expense, net (16.9 ) (15.9 ) (71.2 ) (13.0 ) Income (loss) before provision for income taxes 1,224.1 1,179.2 (888.0 ) 3,232.2 Provision for income taxes 178.7 143.9 560.6 581.4 Net income (loss) $ 1,045.4 $ 1,035.3 $ (1,448.6 ) $ 2,650.8 Net income (loss) per common share: Basic $ 4.05 $ 4.01 $ (5.61 ) $ 10.29 Diluted $ 4.01 $ 3.97 $ (5.61 ) $ 10.18 Shares used in per share calculations: Basic 258.0 258.0 258.1 257.7 Diluted 261.0 260.6 258.1 260.4 Vertex Pharmaceuticals Incorporated Product Revenues (in millions)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 TRIKAFTA/KAFTRIO $ 2,585.0 $ 2,274.3 $ 7,517.8 $ 6,611.4 Other product revenues 186.9 209.2 590.3 740.1 Product revenues, net $ 2,771.9 $ 2,483.5 $ 8,108.1 $ 7,351.5 Vertex Pharmaceuticals Incorporated Reconciliation of GAAP to Non-GAAP Financial Information (in millions, except percentages)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 GAAP cost of sales $ 392.6 $ 318.7 $ 1,107.1 $ 894.2 Stock-based compensation expense (1.9 ) (1.7 ) (5.5 ) (5.4 ) Intangible asset amortization expense (5.0 ) — (15.1 ) — Non-GAAP cost of sales $ 385.7 $ 317.0 $ 1,086.5 $ 888.8 GAAP research and development expenses $ 875.9 $ 810.0 $ 2,631.6 $ 2,338.3 Stock-based compensation expense (111.0 ) (81.1 ) (327.5 ) (231.9 ) Intangible asset amortization expense (0.9 ) — (0.9 ) — Acquisition-related costs (3) — (2.9 ) (172.3 ) (8.5 ) Non-GAAP research and development expenses $ 764.0 $ 726.0 $ 2,130.9 $ 2,097.9 GAAP selling, general and administrative expenses $ 371.8 $ 263.8 $ 1,086.7 $ 767.5 Stock-based compensation expense (71.7 ) (48.1 ) (197.7 ) (135.3 ) Acquisition-related costs (3) — — (36.5 ) — Non-GAAP selling, general and administrative expenses $ 300.1 $ 215.7 $ 852.5 $ 632.2 Combined non-GAAP R&D and SG&A expenses $ 1,064.1 $ 941.7 $ 2,983.4 $ 2,730.1 GAAP other expense, net $ (16.9 ) $ (15.9 ) $ (71.2 ) $ (13.0 ) Decrease in fair value of strategic investments 10.8 6.2 50.5 0.2 Non-GAAP other expense, net $ (6.1 ) $ (9.7 ) $ (20.7 ) $ (12.8 ) GAAP provision for income taxes $ 178.7 $ 143.9 $ 560.6 $ 581.4 Tax adjustments (1) 104.0 112.9 283.8 159.2 Non-GAAP provision for income taxes $ 282.7 $ 256.8 $ 844.4 $ 740.6 GAAP effective tax rate 14.6 % 12.2 % (63.1 )% 18.0 % Non-GAAP effective tax rate 19.8 % 19.4 % (1,038.6 )% 20.5 % Vertex Pharmaceuticals Incorporated Reconciliation of GAAP to Non-GAAP Financial Information (continued) (in millions, except per share amounts)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 GAAP operating income (loss) $ 1,116.3 $ 1,038.1 $ (1,258.9 ) $ 2,843.5 Stock-based compensation expense 184.6 130.9 530.7 372.6 Intangible asset amortization expense 5.9 — 16.0 — Increase (decrease) in fair value of contingent consideration 0.3 1.2 0.7 (1.3 ) Acquisition-related costs (3) — 2.9 208.8 8.5 Non-GAAP operating income (loss) $ 1,307.1 $ 1,173.1 $ (502.7 ) $ 3,223.3 GAAP net income (loss) $ 1,045.4 $ 1,035.3 $ (1,448.6 ) $ 2,650.8 Stock-based compensation expense 184.6 130.9 530.7 372.6 Intangible asset amortization expense 5.9 — 16.0 — Decrease in fair value of strategic investments 10.8 6.2 50.5 0.2 Increase (decrease) in fair value of contingent consideration 0.3 1.2 0.7 (1.3 ) Acquisition-related costs (3) — 2.9 208.8 8.5 Total non-GAAP adjustments to pre-tax income (loss) 201.6 141.2 806.7 380.0 Tax adjustments (1) (104.0 ) (112.9 ) (283.8 ) (159.2 ) Non-GAAP net income (loss) $ 1,143.0 $ 1,063.6 $ (925.7 ) $ 2,871.6 Net income (loss) per diluted common share: GAAP $ 4.01 $ 3.97 $ (5.61 ) $ 10.18 Non-GAAP $ 4.38 $ 4.08 $ (3.59 ) $ 11.03 Shares used in diluted per share calculations: GAAP and Non-GAAP 261.0 260.6 258.1 260.4 Notes 1: In the three and nine months ended September 30, 2024 and 2023, “Tax adjustments” included the estimated income taxes related to non-GAAP adjustments to the company's pre-tax income (loss), discrete benefits related to prior tax years resulting from R&D tax credit studies that were completed in the third quarter of each year and excess tax benefits related to stock-based compensation. 2: The difference between the company’s full-year 2024 combined GAAP R&D and SG&A expenses and combined non-GAAP R&D and SG&A expenses guidance relates primarily to $600 million to $700 million of stock-based compensation expense and $209 million of compensation expense primarily related to cash-settled unvested Alpine equity awards. 3: In the nine months ended September 30, 2024, “Acquisition-related costs” were primarily related to compensation expense associated with cash-settled unvested Alpine equity awards. Vertex Pharmaceuticals Incorporated Condensed Consolidated Balance Sheets (in millions)(unaudited) September 30, 2024 December 31, 2023 Assets Cash, cash equivalents and marketable securities $ 6,524.5 $ 11,218.3 Accounts receivable, net 1,750.6 1,563.4 Inventories 1,079.8 738.8 Prepaid expenses and other current assets 449.2 623.7 Total current assets 9,804.1 14,144.2 Property and equipment, net 1,117.8 1,159.3 Goodwill and intangible assets, net 1,919.6 1,927.9 Deferred tax assets 2,308.9 1,812.1 Operating lease assets 1,396.1 293.6 Long-term marketable securities 4,703.5 2,497.8 Other long-term assets 990.2 895.3 Total assets $ 22,240.2 $ 22,730.2 Liabilities and Shareholders' Equity Accounts payable and accrued expenses $ 3,615.5 $ 3,020.2 Other current liabilities 357.6 527.2 Total current liabilities 3,973.1 3,547.4 Long-term finance lease liabilities 114.0 376.1 Long-term operating lease liabilities 1,588.9 348.6 Other long-term liabilities 933.3 877.7 Shareholders' equity 15,630.9 17,580.4 Total liabilities and shareholders' equity $ 22,240.2 $ 22,730.2 Common shares outstanding 257.7 257.7 About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X. Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements that are subject to risks, uncertainties and other factors. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including all statements regarding the intent, belief, or current expectation of Vertex and members of the Vertex senior management team. Forward-looking statements are not purely historical and may be accompanied by words such as “anticipates,” “may,” “forecasts,” “expects,” “intends,” “plans,” “potentially,” “believes,” “seeks,” “estimates,” and other words and terms of similar meaning. Such statements include, without limitation, Dr. Kewalramani's statements in this press release, the information provided regarding future financial performance and operations, the section captioned “Full-Year 2024 Financial Guidance” and statements regarding (i) expectations for Vertex’s continued growth in CF, including through new approvals and reimbursements for the treatment of younger patients, (ii) the beliefs regarding anticipated benefits of CASGEVY, expectations for increasing numbers of patients initiating cell collection, and expectations with respect to international access and reimbursement for CASGEVY, (iii) expectations regarding the potential benefits and commercial success of suzetrigine for the treatment of moderate-to-severe acute pain, including beliefs regarding the efficacy and safety of suzetrigine, and beliefs that suzetrigine has potential to provide effective pain relief without the limitations of opioids and other available medicines, (iv) expectations and status of the potential near-term commercial launch of the vanzacaftor triple, and plans to continue to advance new oral small molecule combination therapies for the treatment of CF, (v) expectations for VX-522, including the potential benefits of this nebulized mRNA therapy and expectations to complete the Phase 1/2 study and share data in the first half of 2025, (vi) expectations regarding the SCD and TDT program, including expectations that a gentler conditioning for CASGEVY could broaden the eligible patient population, (vii) plans with respect to the studies of the intravenous and oral formulation of VX-993 for the treatment of acute pain, (viii) expectations regarding PNP patient populations, expectations to share results from the Phase 2 study of suzetrigine in LSR by the end of the year, and plans to continue to develop NaV1.8 and NaV1.7 inhibitors for both acute pain and PNP, (ix) expectations regarding the potential benefits of the AMKD program, including plans for the global Phase 2/3 pivotal clinical trial evaluating inaxaplin in patients with AMKD, (x) expectations with respect to povetacicept, including beliefs about its potential benefits and therapeutic scope, study designs, expectations that the interim analysis of this study may serve as the basis to seek accelerated approval in U.S., and beliefs with respect to updated data from the RUBY3 Phase 1b/2 basket study, as presented at a recent medical conference, (xi) expectations regarding the T1D programs, including the status of each of the studies evaluating VX-880 and VX-264 and the expectations to share initial data from the VX-264 study in 2025, (xii) expectations for the potential benefits and clinical status of VX-670 for the treatment in people with DM1, and (xiii) expectations regarding the ADPKD program, including the potential benefits of VX-407 and beliefs regarding the targeted patient population. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that the company's expectations regarding its 2024 full-year product revenues, expenses and effective tax rates may be incorrect (including because one or more of the company's assumptions underlying its expectations may not be realized), that the company may not be able to receive adequate reimbursement for CASGEVY on the expected timeline, or at all, that we are unable to successfully obtain approval or commercialize suzetrigine as a treatment for acute pain or the vanzacaftor triple for CF, that external factors may have different or more significant impacts on the company's business or operations than the company currently expects, that data from preclinical testing or clinical trials, especially if based on a limited number of patients, may not be indicative of final results or available on anticipated timelines, that patient enrollment in the company’s trials may be delayed, that the company may not realize the anticipated benefits from collaborations with third parties, that data from the company's development programs may not support registration or further development of its potential medicines in a timely manner, or at all, due to safety, efficacy or other reasons, and that anticipated commercial launches may be delayed, if they occur at all. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Vertex’s business, particularly those risks listed under the heading “Risk Factors” and the other cautionary factors discussed in Vertex’s periodic reports filed with the SEC, including Vertex’s annual report on Form 10-K for the year ended December 31, 2023, and its quarterly reports on Form 10-Q and current reports on Form 8-K, all of which are filed with the Securities and Exchange Commission (SEC) and available through the company's website at www.vrtx.com and on the SEC’s website at www.sec.gov . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. Conference Call and Webcast The company will host a conference call and webcast at 4:30 p.m. ET. To access the call, please dial (833) 630-2124 (U.S.) or +1(412) 317-0651 (International) and reference the “ Vertex Pharmaceuticals Third Quarter 2024 Earnings Call.” The conference call will be webcast live and a link to the webcast can be accessed through Vertex's website at www.vrtx.com in the "Investors" section. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company's website. (VRTX-E)

▎药明康德内容团队编辑 今年年初，行业媒体Evaluate针对2024年生物医药产业趋势发布了一项分析报告，对2024年可能获批上市的潜在重磅疗法进行了预测。时光匆匆，转眼已经来到了2024年的第四季度，年初这份榜单上的10款疗法中已有8款获得了FDA的批准，其中包括FDA批准的首款非酒精性脂肪性肝炎（NASH）疗法Rezdiffra，数十年来首个治疗精神分裂症的新机制药物KarXT，全球首款端粒酶抑制剂Rytelo，20多年来具有新作用机制、用于慢性阻塞性肺病（COPD）维持治疗的首个吸入式疗法Ohtuvayre等等。这些疗法的获批标志着生物医药领域的重大进步，更重要的是，它们满足了很多此前没有适合的治疗方法患者的迫切需求，也为广大患者带来了疗效更好或使用更便捷的治疗选择。 图片来源：药明康德内容团队根据公开资料制表 除了上述提到的几款疗法，我们同样期待着未来有更多的新药、好药及早被开发出来，尽快送到需要的患者手中，给他们带去新的希望。在今天的文章中，药明康德内容团队将根据多家行业媒体公布的行业报告，盘点近期还有哪些潜在重磅疗法有望获批，以及还有哪些可能对整个行业产生显著影响的研发管线值得关注。 近期有望获批的潜在重磅疗法 据公开信息，2024年第四季度至明年1月，有4款潜在重磅疗法有望获得FDA的监管决定，包括1款抗体偶联药物（ADC）和3款小分子疗法，涉及的适应症包括非小细胞肺癌（NSCLC）、伴有心肌病的转甲状腺素蛋白介导的淀粉样变性（ATTR-CM）、囊性纤维化和急性疼痛。 图片来源：药明康德内容团队根据公开资料制表 疗法名称：datopotamab deruxtecan（Dato-DXd） 研发机构：阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo） 治疗疾病：局部晚期或转移性非鳞状NSCLC Datopotamab deruxtecan是一种由人源化、靶向Trop2的单克隆抗体与创新DNA拓扑异构酶I抑制剂（DXd）连接的在研ADC。DXd具有独特的作用机制，与常见化疗药物伊立替康（irinotecan）相比，活性提高10倍。而且此药物具有很强渗透细胞膜的能力，让它们在杀伤吞入ADC的癌细胞之后，能够杀死附近的癌细胞，产生“旁观者效应”（bystander effect）。 该疗法的上市申请主要基于关键TROPION-Lung01临床3期试验的结果。与目前的标准治疗多西他赛（docetaxel）相比，接受datopotamab deruxtecan治疗的局部晚期或转移性NSCLC患者在双重主要终点之一的无进展生存期（PFS）上显示出统计学上的显著改善，这些患者之前至少接受过一种先前疗法。根据新闻稿，如果获得批准，该疗法将会是首个获批用于治疗肺癌患者的Trop2靶向ADC疗法。除了非小细胞肺癌，datopotamab deruxtecan的另一项针对此前已接受过前期全身治疗的无法切除/转移性HR+、HER2-乳腺癌成人患者的生物制品许可申请（BLA）也在正接受美国FDA的审评。 疗法名称：acoramidis 研发机构：BridgeBio Pharma 治疗疾病：伴有心肌病的转甲状腺素蛋白介导的淀粉样变性 Acoramidis是一种新一代口服、强效的转甲状腺素蛋白（TTR）小分子稳定剂。它旨在模拟具有保护作用的TTR T119M突变的功能，维持TTR蛋白的正常四聚体构象，防止具有毒性的淀粉样蛋白的产生，开发用以治疗ATTR-CM患者。BridgeBio此前公布的结果显示，acoramidis治疗使血清TTR水平在治疗第28天显著增加且维持稳定，并与ATTR-CM参与者在第30个月时降低的总死亡率（ACM）、心血管死亡率（CVM）和心血管住院率（CVH）风险相关。该疗法被行业媒体Evaluate评估为2024年可能获批上市的关键疗法。BridgeBio公司此前的新闻稿也表示，acoramidis有潜力成为重磅疗法。 ▲Acoramidis作用机制（图片来源：参考资料[2]） 疗法名称：vanzacaftor 研发机构：Vertex Pharmaceuticals 治疗疾病：囊性纤维化 Vanzacaftor是一种小分子囊性纤维化跨膜传导调节因子（CFTR）调节剂。Vanzacaftor/tezacaftor/deutivacaft正作为治疗囊性纤维化的下一代三联疗法被开发。Vanzacaftor和tezacaftor旨在通过靶向CFTR蛋白的加工和运输缺陷，增加细胞表面成熟蛋白的数量。Deutivacaftor旨在使细胞表面的CFTR蛋白保持更长时间的开放，以改善穿过细胞膜的盐和水的流动，有助于水合和清除气道中的黏液。此前公布的2期临床试验结果表明，该三联组合疗法有望恢复CFTR蛋白功能，为患者带来临床益处。近期，行业媒体Evaluate发布的盘点文章中将这款疗法列为潜在重磅疗法。目前，vanzacaftor/tezacaftor/deutivacaftor的上市申请已被FDA和欧洲药品管理局接受。 ▲Vanzacaftor分子结构（图片来源：PubChem） 疗法名称：Suzetrigine（VX-548） 研发机构：Vertex Pharmaceuticals 治疗疾病：中度至重度急性疼痛 Suzetrigine是一种口服选择性NaV1.8抑制剂，与其它NaV离子通道相比，它对NaV1.8具有高度选择性。NaV1.8是在外周神经系统的痛觉信号传导中起到关键性作用的电压门控钠通道。它是经过遗传学验证的疼痛治疗靶点。Vertex的策略是通过选择性抑制NaV1.8，开发新的药物类型。与阿片类药物相比，此类药物可能在提供更好镇痛效果的同时，避免上瘾等副作用。此前，FDA已授予suzetrigine优先审评资格，预计在2025年1月30日之前完成审评。新闻稿指出，suzetrigine有望成为二十多年来首个用于治疗急性疼痛的新机制药物。 值得关注的研发管线 除了以上近期有望获批的潜在重磅疗法，根据行业媒体Evaluate和BioPharma Dive的报告，还有一些在研疗法有望对整个行业产生显著影响，并有潜力成为重磅。按针对的适应症进行分类，这些疗法多数集中在代谢疾病、自身免疫疾病、癌症以及精神疾病上。值得一提的是，GLP-1相关疗法在入选的研发项目中占据4席，显示了这一领域的研发热度和潜在潜力。 图片来源：药明康德内容团队根据公开资料制表 CagriSema为GLP-1受体激动剂司美格鲁肽与长效胰淀素类似物cagrilintide的固定剂量组合。去年8月公布的2期临床试验结果显示，CagriSema组患者经过32周的治疗后体重下降了15.6%，糖化血红蛋白（HbA1c）水平下降了2.18个百分点。Orforglipron是礼来公司开发的一种每日一次的口服、非肽类GLP-1受体小分子激动剂。该药物的一个显著优势是它是一种非肽分子，这使得它更容易被制造和包装成药片。与同类作用机制的疗法相比，这一特性还可能有助于提高其在患者中的可负担性和可及性。Retatrutide是礼来的在研靶向葡萄糖依赖性促胰岛素多肽、GLP-1和胰高血糖素受体的三重激动剂。在一项2期临床试验中，83%接受12 mg剂量retatrutide治疗的肥胖或超重成人患者在经过24周的治疗后，达成至少15%的体重下降。MariTide是一款潜在“first-in-class”的在研抗体多肽偶联药物，在靶向胃抑制肽受体（GIPR）的单克隆抗体的特定位点上偶联了两个胰高血糖素样肽1类似物，可在激活GLP-1受体的同时抑制GIPR。此前发表的一项1期临床试验结果显示，肥胖患者只需每月一针，接受高剂量MariTide治疗85天后，体重可降低14.5%（约26斤）。值得一提的是，这些患者在停药后150天，仍可维持体重降低11.2%。 行业报告显示，过去12个月间，全球的GLP-1临床候选药物（小分子和肽类）的数量从51个增长到了79个，增速为55%。值得一提的是，药明康德在行业风口到来之前已准确预判需求并落地布局、将产能迅速放大。过去12个月里，药明康德化学业务平台赋能的临床阶段GLP-1项目从10个增长到18个，增长率达到80%，超越行业增速。能够做到这一切的前提是药明康德管理团队富有远见的发展战略，以及与客户的深度合作。 除了GLP-1相关疗法，这些入选的潜在重磅疗法中有一些在近期更新了令人鼓舞的积极临床试验结果。例如，用于治疗杂合体家族性高胆固醇血症的口服、选择性CETP抑制剂obicetrapib达到了3期关键试验的主要终点，显著降低了患者的低密度脂蛋白胆固醇（LDL-C）水平，且疗效可维持达一年。靶向PD-1和VEGF的双特异性抗体ivonescimab一线治疗PD-L1阳性晚期NSCLC的3期临床试验结果显示，与获批重磅免疫检查点抑制剂相比，ivonescimab显著降低了患者的疾病进展或死亡的风险。行业媒体Fierce Pharma发表的文章表示，这一结果具有改变NSCLC一线标准治疗的潜力。CD40L靶向聚乙二醇化抗原结合片段dapirolizumab pegol联用标准疗法治疗中度至重度系统性红斑狼疮（SLE）的3期临床试验也达到了主要终点，患者的疾病活动程度获得了显著改善。期待研发机构和监管机构能够更密切地合作，进一步加快这些创新疗法的监管审评进程，为广大的患者群体带来新的、有效的治疗选择。 近年来，FDA批准的创新疗法数量显著增加，这是初创公司、大型药企共同推动的成果，也反映了全球医药创新加速。在这个过程中，药明康德很荣幸能与全球志同道合的生物医药合作伙伴携手，为一款又一款新药的问世提供从研究（R）、开发（D）、到商业化生产（M）的一体化全流程服务。 在近日举办的2024药明康德投资者开放日上，药明康德联席首席执行官陈民章博士指出，自2017年至今，药明康德已帮助合作伙伴商业化了50个化合物，并在今年上半年也保持这一强劲势头——2024年上半年美国FDA批准的14款小分子药物中，有3款由药明康德化学业务平台支持。而2023年全球销售额前十的小分子药物中，有4款由药明康德化学业务平台服务生产。不仅如此，由行业知名网站“猎药人”从上万个分子中评选出的2023年度10大明星小分子中，有7款由药明康德化学业务平台赋能。 这些以往的成果证明了药明康德作为创新赋能者的能力，也印证了药明康德独特CRDMO模式对公司自身发展以及对行业、客户和患者的价值。对于坚持CRDMO模式的未来，陈民章博士同样充满信心：“相信在未来获批的新疗法中，一定还会有能为患者提供巨大帮助的重磅疗法出现在药明康德赋能的管线里。” 成立二十余年，药明康德在行业发展中始终坚守初心。展望未来，药明康德也希望协助更多的合作伙伴将研究成果一步步转化为临床实际应用，共同实现“让天下没有难做的药，难治的病”这一伟大梦想！ ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] BridgeBio Shares Data on Serum TTR Increase When Switching Participants from Placebo and Tafamidis to Acoramidis in ATTRibute-CM and its Open-Label Extension. Retrieved August 30, 2024, from https://www.globenewswire.com/news-release/2024/08/30/2938591/0/en/BridgeBio-Shares-Data-on-Serum-TTR-Increase-When-Switching-Participants-from-Placebo-and-Tafamidis-to-Acoramidis-in-ATTRibute-CM-and-its-Open-Label-Extension.html [2] BBIO - ATTRibute-CM Detailed Results From ESC Congress 2023. Retrieved August 28, 2023 from https://investor.bridgebio.com/static-files/f3645003-5c8f-4ec2-b943-03bbad0c156e [3] Vertex Announces FDA Acceptance of New Drug Application for Vanzacaftor/Tezacaftor/Deutivacaftor, a Next-In-Class Triple Combination Treatment for Cystic Fibrosis. Retrieved August 28, 2023 from https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-fda-acceptance-new-drug-application#:~:text=Investigational%20vanzacaftor/tezacaftor/deutivacaftor%20was%20granted%20Fast%20Track%20and%20Orphan%20Drug 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新