Dinutuximab

近日，全球特种制药公司SERB Pharmaceuticals宣布完成对抗癌药企Y-mAbs Therapeutics的全面收购，交易总价值达4.12亿美元。此次收购以全现金形式进行。 Y-mAbs 看名字就是跟抗体相关，主要做核药~目前有一个上市产品—— DANYELZA® （那昔妥单抗，naxitamab）是一款单抗产品，靶点为GD2，用于治疗神经母细胞瘤。 GD2靶点上市产品： GD2（二唾液酸神经节苷脂）是神经外胚层起源的肿瘤细胞表达的一种表面抗原，在多种癌症实体的细胞表面过表达，是癌症免疫治疗的合理靶点，达妥西单抗（dinutuximab）和那昔妥单抗（naxitamab）已获FDA批准用于治疗高危NB的维持治疗。达妥西单抗因表达系统不同又有两个产品Dinutuximab beta（CHO细胞表达）和Naxitamab（hu3F8）。 naxitamab和Dinutuximab beta在国内已经上市，没有看到全球销售数据，在国内2022和2021年上市，到2024年国内销售分别在1.4和 2.6以人民币左右，  Naxitamab2024年全球销量大约在2.4亿美元。 其他在研产品如下：进度最快还是GD2靶点的核药Radiopharmaceuticals Pipeline 主要技术平台——SADA PRIT Technology Platform，(SADA，Self-Assembly DisAssembly； PRIT ，Pre-Targeted Radioimmunotherapy) 分子结构是个四具体，如下： 每个单体（~70kDa）各部分功能如下： 进入体内发挥作用，有两步： 第一步结合到肿瘤上，看示意图至少会有两个结合位点结合上去，这样就增加了靶向性，减少器官脱靶~ 没结合上的四聚体药物粉丝会分离成单体，然后代谢~ 第二步：就是核素分子发挥作用了~ 没有看到太具体的技术细节~ 但是理解下来，通过四聚体或者叫做四抗，提高结合能力，避免脱靶，这是主要的核心点。 这点和双抗ADC有异曲同工之处~ 最后一下问题：GD2的在研产品中CART产品比较多大概有26个进入临床研究的产品，抗体药物只有8个。

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced record financial results for the quarter ended June 30, 2025, driven by continued double-digit year-over-year revenue growth in key products such as Tyvaso DPI, Nebulized Tyvaso, Orenitram, and Unituxin. Total revenues in the second quarter of 2025 grew 12 percent year-over-year to a record $798.6 million, compared to $714.9 million in the second quarter of 2024. “Our second quarter yet again produced record-setting results driven by the strength of our foundational commercial business,” said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics. “We continue to believe there is no other biotech company like ours that provides this combination of sales growth and operating cash flow with near- to medium-term catalysts positioned for sustained long-term growth, starting with data from the TETON 2 study of nebulized treprostinil in idiopathic pulmonary fibrosis expected in September that could fundamentally improve options for patients with this progressive, deadly disease with few treatments available. “Equally, our strong financial position, confidence in these upcoming catalysts, and belief in our share price potential has led our Board of Directors to authorize up to $1 billion in share repurchases, affirming our commitment to a robust and balanced capital allocation philosophy.” Michael Benkowitz, President and Chief Operating Officer of United Therapeutics, added, “We’re proud of the continued record performance for Tyvaso DPI, a best-in-class treprostinil dry powder inhaler that allows the flexibility of one breath per cartridge, four times a day, with low inspiratory effort. Further, no other commercially available treprostinil dry powder inhaler has been clinically studied with published data at higher doses1,2 or prescribed by more physicians to more patients than Tyvaso DPI. “We expect continued double digit revenue growth for Tyvaso and total revenues well into the future through strong commercial execution of our existing product portfolio coupled with the potential for our late-stage pipeline in pulmonary fibrosis and pulmonary hypertension.” ________________________________ 1 Spikes, L. A., et al. (2024, October). Long-term outcomes and dosing in the BREEZE study optional extension phase. CHEST, 166(4, Suppl), A6061–A6063. https://doi.org/10.1016/j.chest.2024.06.3583 2 Burger, C.D., et al. Exploratory Efficacy Analysis of INSPIRE Open-Label Extension Study With Inhaled Treprostinil (YUTREPIA™). American Thoracic Society International Conference 2023. https://liquidia.com/static-files/d5275811-d1af-4ac5-80d4-9bb4b7262d74 Second Quarter 2025 Financial Results Key financial highlights include (dollars in millions, except per share data): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Total revenues $ 798.6 $ 714.9 $ 83.7 12 % Net income $ 309.5 $ 278.1 $ 31.4 11 % Net income, per basic share $ 6.86 $ 6.26 $ 0.60 10 % Net income, per diluted share $ 6.41 $ 5.85 $ 0.56 10 % Revenues The table below presents the components of total revenues (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Net product sales: Tyvaso DPI®(1) $ 315.2 $ 258.3 $ 56.9 22 % Nebulized Tyvaso®(1) 154.4 139.9 14.5 10 % Total Tyvaso 469.6 398.2 71.4 18 % Remodulin®(2) 134.7 147.3 (12.6 ) (9 )% Orenitram® 123.9 107.1 16.8 16 % Unituxin® 58.4 51.7 6.7 13 % Adcirca® 6.5 5.7 0.8 14 % Other 5.5 4.9 0.6 12 % Total revenues $ 798.6 $ 714.9 $ 83.7 12 % (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity® Pump. Total Tyvaso revenues grew by 18 percent to $469.6 million in the second quarter of 2025, compared to $398.2 million in the second quarter of 2024. The growth in Tyvaso DPI revenues resulted primarily from an increase in quantities sold of $54.6 million and, to a lesser extent, a price increase, partially offset by higher gross-to-net revenue deductions. The increase in Tyvaso DPI quantities sold was primarily due to continued growth in the number of patients following the product’s launch, including growth in utilization by patients with pulmonary hypertension associated with interstitial lung disease and, to a lesser extent, increased commercial utilization following the implementation of the Medicare Part D benefit redesign under the Inflation Reduction Act (IRA). The growth in Nebulized Tyvaso revenues resulted primarily from an increase in quantities sold and, to a lesser extent, a price increase. The growth in Orenitram revenues resulted primarily from an increase in quantities sold of $10.6 million and, to a lesser extent, a price increase, partially offset by higher gross-to-net revenue deductions. The increase in quantities sold was driven, at least in part, by increased commercial utilization following the implementation of the Medicare Part D benefit redesign under the IRA. The table below presents the breakdown of total revenues between the United States and rest-of-world (ROW) (in millions): Three Months Ended June 30, 2025 2024 U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ 314.8 $ 0.4 $ 315.2 $ 258.3 $ — $ 258.3 Nebulized Tyvaso(1) 140.5 13.9 154.4 130.2 9.7 139.9 Total Tyvaso 455.3 14.3 469.6 388.5 9.7 398.2 Remodulin(2) 113.7 21.0 134.7 122.5 24.8 147.3 Orenitram 123.9 — 123.9 107.1 — 107.1 Unituxin 55.4 3.0 58.4 46.8 4.9 51.7 Adcirca 6.5 — 6.5 5.7 — 5.7 Other 5.0 0.5 5.5 4.6 0.3 4.9 Total revenues $ 759.8 $ 38.8 $ 798.6 $ 675.2 $ 39.7 $ 714.9 (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity Pump. Expenses Cost of sales. The table below summarizes cost of sales by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Category: Cost of sales $ 86.6 $ 75.9 $ 10.7 14 % Share-based compensation expense(1) 1.0 1.9 (0.9 ) (47 )% Total cost of sales $ 87.6 $ 77.8 $ 9.8 13 % (1) See Share-based compensation below. Cost of sales, excluding share-based compensation. Cost of sales for the three months ended June 30, 2025 increased as compared to the same period in 2024, primarily due to an increase in: (1) royalty expense resulting from a growth in revenues; and (2) reserve expense resulting from increased production. Research and development. The table below summarizes the nature of research and development expense by major expense category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Category: External research and development(1) $ 62.4 $ 49.4 $ 13.0 26 % Internal research and development(2) 55.9 44.5 11.4 26 % Share-based compensation expense(3) 8.1 8.6 (0.5 ) (6 )% Other(4) 7.6 37.1 (29.5 ) (80 )% Total research and development expense $ 134.0 $ 139.6 $ (5.6 ) (4 )% (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product. (2) Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities. (3) See Share-based compensation below. (4) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products and adjustments to the fair value of our contingent consideration obligations. Research and development, excluding share-based compensation. Research and development expense for the three months ended June 30, 2025 decreased as compared to the same period in 2024, primarily due to $36.0 million in upfront non-refundable license payments for drug delivery device technologies in 2024, partially offset by: (1) increased expenditures in 2025 related to manufactured organ and organ alternative projects; and (2) a $5.0 million milestone payment made in 2025 for drug delivery device technologies. Selling, general, and administrative. The table below summarizes selling, general, and administrative expense by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Category: General and administrative(1) $ 131.1 $ 113.0 $ 18.1 16 % Impairment of property, plant, and equipment (PP&E) 21.7 — 21.7 NM(2) Sales and marketing 31.0 25.4 5.6 22 % Share-based compensation expense(3) 28.7 39.2 (10.5 ) (27 )% Total selling, general, and administrative expense $ 212.5 $ 177.6 $ 34.9 20 % (1) Excluding impairment of PP&E. See Impairment of PP&E section below. (2) Calculation is not meaningful. (3) See Share-based compensation below. General and administrative, excluding impairment of PP&E and share-based compensation. General and administrative expense for the three months ended June 30, 2025 increased as compared to the same period in 2024, primarily due to: (1) personnel expense due to growth in headcount; and (2) legal expenses related to litigation matters. Impairment of PP&E. During the three months ended June 30, 2025, we recorded a $21.7 million impairment charge to write down the carrying value of certain PP&E. Share-based compensation. The table below summarizes share-based compensation expense by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2025 2024 Category: Stock options $ 11.1 $ 8.1 $ 3.0 37 % Restricted stock units 26.0 19.2 6.8 35 % Share tracking awards plan (STAP) — 21.9 (21.9 ) (100 )% Employee stock purchase plan 0.7 0.5 0.2 40 % Total share-based compensation expense $ 37.8 $ 49.7 $ (11.9 ) (24 )% The decrease in share-based compensation expense for the three months ended June 30, 2025, as compared to the same period in 2024, was primarily due to a decrease in STAP expense, as all remaining STAP awards were exercised during the first quarter of 2025. Income tax expense. Income tax expense for the three months ended June 30, 2025 and 2024 was $98.9 million and $77.2 million, respectively. Our effective income tax rate (ETR) for the three months ended June 30, 2025 and 2024 was 24 percent and 22 percent, respectively. Our ETR for the three months ended June 30, 2025 increased compared to our ETR for the three months ended June 30, 2024, primarily due to a decrease in excess tax benefits from share-based compensation. Webcast We will host a webcast to discuss our second quarter 2025 financial results on Wednesday, July 30, 2025, at 9:00 a.m. Eastern Time. The webcast can be accessed live via our website at https://ir.unither.com/events-and-presentations. An investor presentation is available now, and after the webcast a replay of the webcast will also be available, at the same location on our website. United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun; we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/pbc. Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements related to our share repurchase program, the anticipated timing and outcome of the TETON 2 and TETON 1 clinical trials of Nebulized Tyvaso in idiopathic pulmonary fibrosis, including potential for these studies to improve options for patients with this disease; the anticipated readout of the ADVANCE OUTCOMES clinical trial of ralinepag; our near- to medium-term catalysts positioned for sustained long-term growth; our expectation of continued double digit revenue growth for Tyvaso and total revenues well into the future through strong commercial execution of our existing product portfolio coupled with the potential for our late-stage pipeline in pulmonary fibrosis and pulmonary hypertension; and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of July 30, 2025, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. ORENITRAM, REMODULIN, REMUNITY, TYVASO, TYVASO DPI, and UNITUXIN are registered trademarks of United Therapeutics Corporation and/or its subsidiaries. ADCIRCA is a registered trademark of Eli Lilly and Company. UNITED THERAPEUTICS CORPORATION CONSOLIDATED STATEMENTS OF OPERATIONS (In millions, except per share data) Three Months Ended June 30, 2025 2024 (Unaudited) Total revenues $ 798.6 $ 714.9 Operating expenses: Cost of sales 87.6 77.8 Research and development 134.0 139.6 Selling, general, and administrative 212.5 177.6 Total operating expenses 434.1 395.0 Operating income 364.5 319.9 Interest income 51.3 46.2 Interest expense (7.3 ) (11.6 ) Other (expense) income, net (0.1 ) 0.8 Total other income, net 43.9 35.4 Income before income taxes 408.4 355.3 Income tax expense (98.9 ) (77.2 ) Net income $ 309.5 $ 278.1 Net income per common share: Basic $ 6.86 $ 6.26 Diluted $ 6.41 $ 5.85 Weighted average number of common shares outstanding: Basic 45.1 44.4 Diluted 48.3 47.5 SELECTED CONSOLIDATED BALANCE SHEET DATA (Unaudited, in millions) June 30, 2025 Cash, cash equivalents, and marketable investments $ 4,966.4 Total assets 7,908.0 Total liabilities 734.4 Total stockholders’ equity 7,173.6 Category: Earnings