Graves Ophthalmopathy

$573 million in third quarter global net product sales CIDP global expansion on track, with decisions on approval under review in Japan, Europe, China, and Canada Management to host conference call today at 1:30 PM CET (8:30 AM ET) Regulated information - Inside information October 31, 2024 7:00AM CET Amsterdam, the Netherlands – argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced its third quarter 2024 financial results and provided a business update. “We delivered significant patient impact with VYVGART over the quarter, expanding our gMG footprint and delivering innovation to CIDP patients three months into launch,” said Tim Van Hauwermeiren, Chief Executive Officer of argenx. “We continued to advance our goal of reaching more gMG patients earlier in their treatment journey, supported by VYVGART’s strong safety and efficacy profile, and real-world data showing the ability to meaningfully reduce steroid use. Expanding upon our leadership in gMG, we are now paving the future in CIDP. The strength of our data, combined with execution across the team to reach key stakeholders, contributed to the initial success of our CIDP launch, with more than 300 patients on therapy at the end of the third quarter. There remains significant opportunity ahead as we work towards achieving our Vision 2030, with innovation implemented across our pipeline to deliver transformative outcomes to more patients.” Advancing ‘Vision 2030’ in Third Quarter 2024 Vision 2030 is the next phase in argenx’s long-term commitment to transform the treatment of autoimmune diseases by strengthening its leadership in FcRn biology, investing in its continuous pipeline of differentiated antibody candidates, and scaling in a disciplined way to ensure innovation remains core to the argenx mission. As a part of this vision, argenx plans to reach at least 50,000 patients globally, advance the pipeline to achieve 10 labeled indications, and bring five new molecules into Phase 3 by 2030. Reaching 50,000 Patients Globally by 2030 VYVGART® (efgartigimod alfa-fcab) is a first-in-class antibody fragment targeting FcRn and is now approved for both intravenous use and subcutaneous injection (SC) (efgartigimod alfa and hyaluronidase-qvfc) in three indications, including generalized myasthenia gravis (gMG) globally, primary immune thrombocytopenia (ITP) in Japan (IV only), and chronic inflammatory demyelinating polyneuropathy (CIDP) in the U.S. (SC only). Generated global net product revenues (inclusive of both VYVGART and VYVGART SC) of $573 million in the third quarter of 2024Multiple VYVGART regulatory submissions completed or underway for gMG, including: Swissmedic approved VYVGART for the treatment of gMG in SwitzerlandRegulatory decisions on approval expected in Australia and Saudi Arabia in 2024, and South Korea in 2025 Multiple VYVGART SC regulatory submissions under review or planned for CIDP, including: Regulatory submissions completed in Japan, Europe, and China with decisions on approval expected in 2025Regulatory submission to be completed in Canada by end of 2024 VYVGART now reimbursed in 11 countries in Europe, with new agreements in place in France, Luxembourg, and BelgiumFDA review of VYVGART SC pre-filled syringe (PFS) for gMG and CIDP ongoing with Prescription Drug User Fee Act (PDUFA) target action date of April 10, 2025 Advancing Pipeline to Achieve 10 Labeled Indications by 2030 argenx continues to demonstrate breadth and depth within its immunology pipeline, advancing multiple pipeline-in-a-product candidates. argenx is solidifying its leadership in FcRn biology, with efgartigimod currently in development in 15 indications. argenx is also advancing its first-in-class C2 inhibitor, empasiprubart, which is being evaluated in multifocal motor neuropathy (MMN), delayed graft function (DGF), dermatomyositis (DM), and CIDP. In addition, argenx is evaluating ARGX-119, a muscle-specific kinase (MuSK) agonist in both congenital myasthenic syndrome (CMS) and amyotrophic lateral sclerosis (ALS). Registrational studies ongoing of efgartigimod in thyroid eye disease (TED)Registrational studies ongoing to support label-expansion into broader MG, including ADAPT SERON in seronegative gMG and ADAPT OCULUS in ocular MGRegistrational study in primary Sjögren’s disease (SjD) on track to start by end of 2024Confirmatory study of efgartigimod in primary ITP to start by end of 2024 to enable registration in U.S.Topline data from seamless Phase 2/3 ALKIVIA study evaluating efgartigimod across three myositis subsets (immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and DM) expected by end of 2024Update on BALLAD study development plan evaluating efgartigimod in bullous pemphigoid (BP) expected by end of 2024Decision made to discontinue development of efgartigimod in membranous nephropathy (MN); proof-of concept study ongoing with efgartigimod in lupus nephritis (LN)Proof-of-concept study ongoing with efgartigimod in antibody mediated rejection (AMR), with systemic sclerosis (SSc) to start by end of 2024Registrational study of empasiprubart in MMN to start by end of 2024Additional proof-of-concept studies of empasiprubart ongoing, including VARVARA study in DGF and EMPACIFIC study in DMRegistrational study of empasiprubart in CIDP to start in 2025Ongoing Phase 1b/2a studies of ARGX-119 to assess early signal in patients with CMS and ALS Investing in Immunology Innovation Program to Support Five New Molecules in Phase 3 by 2030 argenx continues to invest in its Immunology Innovation Program (IIP) to drive long-term sustainable pipeline growth. Through the IIP, four new pipeline candidates have been nominated, including: ARGX-213, targeting FcRn and further solidifying argenx’s leadership in this new class of medicine; ARGX-121, a first-in-class molecule targeting IgA; ARGX-109, targeting IL-6, which plays an important role in inflammation, and ARGX-220, a first-in-class sweeping antibody for which the target has not yet been disclosed. Phase 1 studies of ARGX-213 and ARGX-121 expected to start in second half of 2025Investigational new drug (IND) applications for ARGX-220 and ARGX-109 on track to be filed by end of 2025 THIRD QUARTER 2024 FINANCIAL RESULTS argenx SE UNAUDITED CONDENSED CONSOLIDATED INTERIM STATEMENTS OF PROFIT OR LOSS Three Months Ended Nine Months Ended September 30 September 30(in thousands of $ except for shares and EPS) 2024 2023 2024 2023Product net sales $ 572,997 $ 329,097 $ 1,448,915 $ 816,432 Collaboration revenue 239 692 2,905 3,047 Other operating income 15,642 10,050 38,999 31,275 Total operating income $ 588,878 $ 339,839 $ 1,490,819 $ 850,754 Cost of sales $ (59,072) $ (35,999) $ (154,633) $ (78,358)Research and development expenses (235,940) (191,755) (686,195) (553,119)Selling, general and administrative expenses (277,698) (191,930) (769,392) (503,079)Loss from investment in a joint venture (1,981) (743) (5,294) (2,623)Total operating expenses $ (574,691) $ (420,427) $ (1,615,514) $ (1,137,179) Operating profit/(loss) $ 14,187 $ (80,588) $ (124,695) $ (286,425) Financial income $ 40,586 $ 30,049 $ 118,414 $ 67,078 Financial expense (676) (231) (1,760) (626)Exchange gains/(losses) 33,927 (32,509) 6,712 (23,345) Profit/(loss) for the period before taxes $ 88,024 $ (83,279) $ (1,329) $ (243,318)Income tax (expense)/benefit $ 3,386 $ 10,637 $ 60,208 $ 47,437 Profit/(loss) for the period $ 91,410 $ (72,642) $ 58,879 $ (195,881)Profit/(loss) for the period attributable to: Owners of the parent $ 91,410 $ (72,642) $ 58,879 $ (195,881)Weighted average number of shares outstanding 60,087,498 58,128,233 59,633,179 56,512,254 Basic profit/(loss) per share (in $) 1.52 (1.25) 0.99 (3.47)Diluted profit/(loss) per share (in $) 1.39 (1.25) 0.91 (3.47)Net increase in cash, cash equivalents and current financial assets compared to year-end 2023 and 2022 $ 194,523 $ 993,035 Cash and cash equivalents and current financial assets at the end of the period $ 3,374,367 $ 3,185,583 DETAILS OF THE FINANCIAL RESULTS Total operating income for the third quarter and year-to-date in 2024 was $589 million and $1,491 million, respectively, compared to $340 million and $851 million for the same periods in 2023, and mainly consists of: Product net sales of VYVGART for the three months ended and nine months ended September 30, 2024, were $573 million and $1,449 million, compared to $329 million and $816 million for the same periods in 2023.Other operating income for the third quarter and year-to-date in 2024 was $16 million and $39 million, respectively, compared to $10 million, and $31 million for the same periods in 2023. The other operating income for the three and nine months ended September 30, 2024 primarily relates to research and development tax incentives and payroll tax rebates. Total operating expenses for the third quarter and year-to-date in 2024 were $575 million and $1,616 million, respectively, compared to $420 million and $1,137 million for the same periods in 2023, and mainly consists of: Cost of sales for the third quarter and year-to-date in 2024 was $59 million and $155 million, respectively, compared to $36 million and $78 million for the same periods in 2023. The cost of sales was recognized with respect to the sale of VYVGART and VYVGART Hytrulo.Research and development expenses for the third quarter and year-to-date in 2024 were $236 million and $686 million, respectively, compared to $192 million and $553 million for the same periods in 2023. The research and development expenses mainly relate to external research and development expenses and personnel expenses incurred in the clinical development of efgartigimod in various indications and the expansion of other clinical and preclinical pipeline candidates.Selling, general and administrative expenses for the third quarter and year-to-date in 2024 were $278 million and $769 million, respectively, compared to $192 million and $503 million for the same periods in 2023. The selling, general and administrative expenses mainly relate to professional and marketing fees linked to global commercialization of VYVGART and VYVGART Hytrulo, and personnel expenses. Financial income for the third quarter and year-to-date in 2024 was $41 million and $118 million, respectively, compared to $30 million and $67 million for the same periods in 2023. The increase in financial income is mainly due to an increase in interest income on current financial assets and cash and cash equivalents. Exchange gains for the third quarter and year-to-date in 2024 were $34 million and $7 million respectively, respectively, compared to $(33) million and $(23) million of exchange losses for the same periods in 2023. Exchange gains/losses are mainly attributable to unrealized exchange rate gains or losses on the cash, cash equivalents and current financial assets position in Euro. Income tax for the third quarter and year-to-date in 2024 was $3 million and $60 million of tax benefit, respectively, compared to $11 million and $47 million of tax benefit for the same periods in 2023. Tax benefit for the nine months ended September 30, 2024 consists of $29 million of income tax expense and $89 million of deferred tax income, compared to $24 million of income tax expense and $71 million of deferred tax income for the comparable prior period. Net income for the three and nine month periods ended September 30, 2024, was $91 million and $59 million, respectively, compared to a net loss of $(73) million and $(196) million over the prior year periods. On a per weighted average share basis, the earnings per share was $0.99 for the nine months ended September 30, 2024 and a net loss per share of $(3.47) for the nine months ended September 30, 2023. Cash, cash equivalents and current financial assets totaled $3.4 billion as of September 30, 2024, compared to $3.2 billion as of December 31, 2023. The increases in cash and cash equivalents and current financial assets over the period was from financing activities due to the exercise of stock options which is offset by net cash flows used in operating and investing activities. FINANCIAL GUIDANCE With the increase in cash, cash equivalents and current financial assets in the quarter and year-to-date, the previously issued cash guidance no longer applies. The financial guidance on the combined selling, general and administrative expenses and research and development expenses remains unchanged at approximately $2 billion. EXPECTED 2024 FINANCIAL CALENDAR February 27, 2025: Full-year 2024 financial results and 4Q 2024 business update CONFERENCE CALL DETAILS The third quarter 2024 financial results and business update will be discussed during a conference call and webcast presentation today at 1:30 pm CET/8:30 am ET. A webcast of the live call and replay may be accessed on the Investors section of the argenx website at argenx.com/investors. Dial-in numbers: Please dial in 15 minutes prior to the live call. Belgium 32 800 50 201France 33 800 943355Netherlands 31 20 795 1090United Kingdom 44 800 358 0970United States 1 888 415 4250Japan 81 3 4578 9081Switzerland 41 43 210 11 32 About argenx argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first approved neonatal Fc receptor (FcRn) blocker in the U.S., Japan, Israel, the EU, the UK, China and Canada. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visit www.argenx.com, and follow us on LinkedIn, X/Twitter, Instagram, Facebook, and YouTube. For further information, please contact: Media: Ben Petokbpetok@argenx.com Investors:Alexandra Roy (US)aroy@argenx.com Lynn Elton (EU)lelton@argenx.com Forward-looking Statements The contents of this announcement include statements that are, or may be deemed to be, “forward-looking statements.” These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “aim,” “achieve,” “advance,” “bring,” “complete,” “expect,” “initiate,” “plan,” “reach,” “start,” “support,” “to be,” or “will,” and include statements argenx makes regarding its goal to reach more gMG patients in an early-line setting; its growth opportunity; its Vision 2030 plan, including (1) transforming the treatment of autoimmune diseases by strengthening its leadership in FcRn biology, (2) investing in its continuous pipeline of differentiated antibody candidates, (3) scaling in a disciplined way to ensure innovation, and (4) reaching 50,000 patients globally with an argenx medicine, 10 labeled indications across all approved assets, and five new molecules in Phase 3 development; the advancement of anticipated clinical development, data readouts and regulatory milestones and plans, including (1) the anticipated timing of additional VYVGART regulatory decisions on approval for gMG in Australia, Saudi Arabia, and South Korea, (2) the anticipated timing of VYVGART SC regulatory submissions for CIDP, including decisions on approval in China, Japan, and Europe and an anticipated regulatory submission filing in Canada, (3) the anticipated timing of the initiation of a registrational study for efgartigimod in primary SjD, (4) the anticipated timing of a confirmatory study of efgartigimod in primary ITP, (5) the anticipated timing of topline data from Phase 2/3 ALKIVIA study evaluating efgartigimod across three myositis subsets, (6) the anticipated timing of an update on the BALLAD study development plan evaluating efgartigimod in BP, (7) the anticipated timing of proof-of-concept study data for efgartigimod in LN, (8) the anticipated timing of the initiation of a study on efgartimod in SSc, (9) the anticipated timing of the initiation of a registrational study of empasiprubart for MMN, (9) the anticipated timing of the initiation of a registrational study of empasiprubart in CIDP, (10) the anticipated timing of the initiation of Phase 1 studies of ARGX-213 and ARGX-121, (11) the anticipated timing of the filing of investigational new drug applications for ARGX-220 and ARGX-109; the advancement of empasiprubart; its 2024 selling, general and administrative expenses and research and development expenses; the anticipated timing of releases of future financial results and business updates; and its goal of translating immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. argenx’s actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors, including the results of argenx's clinical trials; expectations regarding the inherent uncertainties associated with the development of novel drug therapies; preclinical and clinical trial and product development activities and regulatory approval requirements in products and product candidates; the acceptance of argenx's products and product candidates by patients as safe, effective and cost-effective; the impact of governmental laws and regulations on our business; disruptions caused on our reliance of third parties suppliers, service provides and manufacturing; inflation and deflation and the corresponding fluctuations in interest rates; and regional instability and conflicts. A further list and description of these risks, uncertainties and other risks can be found in argenx’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in argenx’s most recent annual report on Form 20-F filed with the SEC as well as subsequent filings and reports filed by argenx with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. argenx undertakes no obligation to publicly update or revise the information in this press release, including any forward-looking statements, except as may be required by law.

THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the third quarter of 2024. "Strong growth in sales and earnings this quarter reflects the momentum we're building throughout our business. We continue to invest heavily in our rapidly advancing pipeline, with a focus on delivering innovative therapies across our core therapeutic areas," said Robert A. Bradway, chairman and chief executive officer. Key results include: For the third quarter, total revenues increased 23% to $8.5 billion in comparison to the third quarter of 2023. Product sales grew 24%, driven by 29% volume growth, partially offset by 2% lower net selling price. Excluding sales from our Horizon Therapeutics (Horizon) acquisition, product sales grew 8%, driven by volume growth of 12%. Ten products delivered at least double-digit sales growth in the third quarter, including Repatha® (evolocumab), TEZSPIRE® (tezepelumab-ekko), BLINCYTO® (blinatumomab), EVENITY® (romosozumab-aqqg), and TAVNEOS® (avacopan). Our performance included $1.2 billion of sales from our rare disease products, driven by several first-in-class, early-in-lifecycle medicines, including TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase), UPLIZNA® (inebilizumab-cdon), and TAVNEOS® (avacopan). GAAP earnings per share (EPS) increased 62% from $3.22 to $5.22, driven by mark-to-market gains on our BeiGene, Ltd. (BeiGene) equity investment and higher revenues, partially offset by higher operating expenses, including amortization expense from Horizon-acquired assets and incremental expenses from Horizon. GAAP operating income remained relatively unchanged at $2.0 billion, and GAAP operating margin decreased 5.8 percentage points to 25.1%. Non-GAAP EPS increased 13% from $4.96 to $5.58, driven by higher revenues, partially offset by higher operating expenses, including incremental expenses from Horizon, and interest expense. Non-GAAP operating income increased from $3.4 billion to $4.0 billion, and non-GAAP operating margin decreased 2.4 percentage points to 49.6%. The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis" and "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance General Medicine Repatha® (evolocumab) sales increased 40% year-over-year to $567 million in the third quarter, driven by 41% volume growth and 8% favorable changes to estimated sales deductions, partially offset by 10% lower net selling price. EVENITY® (romosozumab-aqqg) sales increased 30% year-over-year to $399 million in the third quarter, driven by volume growth. Prolia® (denosumab) sales increased 6% year-over-year to $1.0 billion in the third quarter, driven by 9% volume growth, partially offset by lower inventory levels. Oncology BLINCYTO® (blinatumomab) sales increased 49% year-over-year to $327 million in the third quarter, primarily driven by volume growth. Vectibix® (panitumumab) sales increased 12% year-over-year to $282 million in the third quarter, primarily driven by volume growth. KYPROLIS® (carfilzomib) sales increased 8% year-over-year to $378 million in the third quarter, primarily driven by volume growth outside the U.S. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 88% year-over-year to $98 million in the third quarter, driven by volume growth and favorable changes to estimated sales deductions. XGEVA® (denosumab) sales increased 4% year-over-year to $541 million in the third quarter, driven by higher net selling price. Nplate® (romiplostim) sales increased 9% year-over-year to $456 million in the third quarter. U.S. government orders were $128 million in Q3'24 compared to $142 million in Q3'23. Excluding these U.S. government orders, Nplate sales grew 18% year-over-year in the third quarter, driven by 14% volume growth and higher net selling price. IMDELLTRA™ (tarlatamab-dlle) generated $36 million of sales in the third quarter. Sales increased 200% quarter-over-quarter, driven by volume growth. IMDELLTRA is the first and only FDA-approved bispecific T-cell engager (BiTE ®) therapy for the treatment of extensive-stage small cell lung cancer (ES-SCLC). MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year to $195 million in the third quarter. Going forward, we expect continued sales erosion driven by competition. Inflammation TEZSPIRE® (tezepelumab-ekko) sales increased 67% year-over-year to $269 million in the third quarter, driven by volume growth. Otezla® (apremilast) sales decreased 1% year-over-year to $564 million in the third quarter, primarily driven by 7% lower net selling price, partially offset by 5% volume growth. Enbrel® (etanercept) sales decreased 20% year-over-year to $825 million in the third quarter, primarily driven by 13% unfavorable changes to estimated sales deductions and 12% lower net selling price. Going forward, we expect continued declining net selling price and relatively flat volumes. AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 9% year-over-year to $166 million in the third quarter. Rare Disease Except for TAVNEOS®, the products listed below were added through the acquisition of Horizon on Oct. 6, 2023. TEPEZZA® (teprotumumab-trbw) generated $488 million of sales in the third quarter. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED). KRYSTEXXA® (pegloticase) generated $310 million of sales in the third quarter. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout. UPLIZNA® (inebilizumab-cdon) generated $106 million of sales in the third quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorder. TAVNEOS® (avacopan) generated $80 million of sales in the third quarter. Sales increased 116% year-over-year, primarily driven by volume growth. TAVNEOS is a first-in-class treatment for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis). Ultra-Rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), QUINSAIR® (levofloxacin) and BUPHENYL® (sodium phenylbutyrate), generated $188 million of sales in the third quarter. Established Products Our established products, which consist of EPOGEN® (epoetin alfa), Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), generated $550 million of sales. Sales decreased 7% year-over-year for the third quarter, driven by volume declines. In the aggregate, we expect the year-over-year volume declines for this portfolio of products to continue. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis for the third quarter: Total Operating Expenses increased 32% year-over-year. Cost of Sales as a percentage of product sales increased 13.0 percentage points driven by higher amortization expense from Horizon acquisition-related assets and, to a lesser extent, higher royalties and profit share. Research & Development (R&D) expenses increased 34% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. Selling, General & Administrative (SG&A) expenses increased 20% primarily driven by commercial expenses related to Horizon-acquired products. Other operating expenses consisted primarily of an impairment charge associated with an IPR&D asset and changes in the fair values of contingent consideration liabilities, both related to our Teneobio, Inc. acquisition from 2021. Operating Margin as a percentage of product sales decreased 5.8 percentage points year-over-year to 25.1%. Tax Rate decreased 2.4 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business, partially offset by quarter-to-date 2024 unrealized gains on our strategic equity investments, primarily BeiGene. On a non-GAAP basis for the third quarter: Total Operating Expenses increased 27% year-over-year. Cost of Sales as a percentage of product sales increased 0.4 percentage points driven by higher royalties and profit share, partially offset by lower manufacturing costs and changes in sales mix. R&D expenses increased 35% driven by higher spend in later-stage clinical programs, marketed product support, and research and early pipeline, including Horizon-acquired programs. SG&A expenses increased 21%, primarily driven by commercial expenses related to Horizon-acquired products. Operating Margin as a percentage of product sales decreased 2.4 percentage points year-over-year to 49.6%. Tax Rate decreased 2.7 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business. Cash Flow and Balance Sheet The Company generated $3.3 billion of free cash flow in the third quarter of 2024 versus $2.5 billion in the third quarter of 2023, driven by business performance and timing of working capital items, partially offset by lower interest income. The Company's third quarter 2024 dividend of $2.25 per share was declared on August 2, 2024, and was paid on September 6, 2024, to all stockholders of record as of August 16, 2024, representing a 6% increase from this same period in 2023. During the third quarter, the Company reduced principal debt outstanding by $2.5 billion. Year-to-date, the Company has reduced principal debt outstanding by $4.5 billion. Cash and investments totaled $9.0 billion and debt outstanding totaled $60.4 billion as of September 30, 2024. 2024 Guidance For the full year 2024, the Company now expects: Total revenues in the range of $33.0 billion to $33.8 billion. On a GAAP basis, EPS in the range of $8.71 to $9.56, and a tax rate in the range of 9.0% to 10.5%. On a non-GAAP basis, EPS in the range of $19.20 to $20.00, and a tax rate in the range of 14.0% to 15.0%. Capital expenditures to be approximately $1.3 billion. Share repurchases not to exceed $500 million. Third Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine MariTide (maridebart cafraglutide, AMG 133) MariTide is a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor. A Phase 2 study of MariTide is ongoing in adults who are living with overweight or obesity, with or without Type 2 diabetes mellitus. Topline data are anticipated in late 2024. Planning for a broad Phase 3 program across multiple indications remains on track. A Phase 2 study investigating MariTide was initiated for the treatment of Type 2 diabetes in patients with and without obesity. AMG 513 A Phase 1 study of AMG 513 was initiated and is enrolling patients living with obesity. Olpasiran (AMG 890) Olpasiran is a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver. The Ocean(a)-Outcomes trial, a Phase 3 cardiovascular outcomes study, is ongoing in patients with atherosclerotic cardiovascular disease and elevated Lp(a). Repatha EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular (CV) events, is ongoing. VESALIUS-CV, a Phase 3 CV outcomes study of Repatha, is ongoing in patients at high CV risk without prior myocardial infarction or stroke. In September data were presented from: a sub-analysis of the FOURIER trial demonstrating that patients with obesity (BMI >35) are at an increased risk of CV events. Repatha treatment of patients with obesity resulted in a reduction in the composite endpoint of CV death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization at 3 years [HR 0.71 (0.59-0.86), and Absolute Risk Reduction = 5.65%] the SLICE-CEA study, the first randomized trial of Repatha in patients with asymptomatic severe high-risk carotid artery stenosis. The study demonstrated that 6 months of Repatha treatment led to significant reductions in lipid rich necrotic core (LRNC) volume (p=0.017) and its components, intraplaque hemorrhage (IPH) (p=0.037) and lipid volume (p=0.023) in the carotid vessels, as assessed by MRI. Oncology IMDELLTRA IMDELLTRA is a first-in-class delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The Company is advancing a comprehensive global clinical development program across extensive-stage and limited-stage small cell lung cancer (SCLC): DeLLphi-304, a Phase 3 study comparing IMDELLTRA with standard of care chemotherapy in second-line extensive-stage small cell lung cancer (ES-SCLC), is ongoing. DeLLphi-305, a Phase 3 study comparing IMDELLTRA and durvalumab with durvalumab alone, is enrolling patients with first-line ES-SCLC. DeLLphi-306, a Phase 3 study comparing IMDELLTRA with placebo following concurrent chemoradiation therapy, is enrolling patients with limited-stage SCLC. DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab, was initiated in patients with second line or later ES-SCLC. DeLLphi-303, a Phase 1b study of IMDELLTRA in combination with a programmed cell death protein ligand-1 (PD-L1) inhibitor +/- carboplatin and etoposide, is ongoing in patients with first-line ES-SCLC. DeLLphi-302, a Phase 1b study of IMDELLTRA in combination with AMG 404 in patients with second-line or later SCLC, is complete. AMG 404 is an anti-programmed cell death protein 1 (PD1) monoclonal antibody. DeLLpro-300, a Phase 1b study of IMDELLTRA in patients with previously treated de novo or treatment-emergent neuroendocrine prostate cancer, is complete. In September, data were presented from: DeLLphi-301, a Phase 2 study of IMDELLTRA where extended follow-up data demonstrated sustained anti-cancer activity and a manageable safety profile in patients with ES-SCLC previously treated with platinum-based chemotherapy. Among 100 patients treated with the 10 mg dose level, the median duration of response was 9.7 months (95% CI, 6.9‒NE) and the median overall survival was 15.2 months. No new safety concerns were identified. DeLLphi-303, a Phase 1b study of IMDELLTRA combined with a PD-L1 inhibitor as first-line ES-SCLC maintenance therapy. With a median follow-up of 10.0 months (range 1.4 - 20.4), IMDELLTRA in combination with a PD-L1 inhibitor, demonstrated a manageable safety profile with durable disease control [median duration of disease control: 9.3 months (95% CI: 5.6–not estimable)] and notable survival outcomes [median PFS 5.6 months (95% CI: 3.6–9.0), 9-month Kaplan-Meier estimate for OS of 88.9%]. BLINCYTO Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy, continues to enroll older adult patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (B-ALL). A Phase 1/2 study of subcutaneous blinatumomab has completed enrollment in the dose-expansion and optimization phase in adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025. Xaluritamig (AMG 509) Xaluritamig is a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1). The Company will initiate a Phase 3 study in post-taxane metastatic castrate resistant prostate cancer (mCRPC) in fourth quarter of 2024. A Phase 1 monotherapy dose-expansion study of xaluritamig is ongoing in patients with mCRPC and has completed enrollment of patients in a reduced monitoring after treatment administration cohort. A fully outpatient treatment cohort continues to enroll patients to further improve administration convenience. A Phase 1 combination of xaluritamig with enzalutamide or abiraterone continues to enroll patients with mCRPC in dose-escalation and dose-expansion respectively. A Phase 1b study evaluating neoadjuvant xaluritamig therapy prior to radical prostatectomy was initiated in patients with newly diagnosed localized intermediate or high–risk prostate cancer. A Phase 1b study was initiated and is now enrolling patients to evaluate xaluritamig in patients with high-risk nonmetastatic hormone-sensitive prostate cancer after definitive therapy. In September results were presented from: a Phase 1 dose exploration cohort evaluating xaluritamig monotherapy in patients with mCRPC where with a median follow-up of 27.9 months, the median OS was 17.7 months across all cohorts. An encouraging PSA90 rate (45.1%) was also observed in high-dose cohorts, and presence of PSA90 response was associated with survival (p = 0.0044), potentially serving as an early indicator for benefit in these patients. a Phase 1 dose-expansion cohort evaluating xaluritamig monotherapy using multiple dosing regimens in patients with mCRPC demonstrated that the 1.5 mg Q2W target dosing regimen is the most favorable efficacy and safety profile and will be the recommended Phase 3 dose and schedule. AMG 193 AMG 193 is a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. A Phase 1/1b/2 study of AMG 193 continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors in the dose-expansion portion of the study. A Phase 1b study of AMG 193 alone or in combination with other therapies is enrolling patients with advanced MTAP-null thoracic malignancies. A Phase 1b study of AMG 193 in combination with other therapies in advanced MTAP-null gastrointestinal, biliary tract, and pancreatic cancers is enrolling patients. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, continues to enroll patients with advanced MTAP-null solid tumors. A Phase 2 study evaluating the efficacy, safety, tolerability, and pharmacokinetics of AMG 193 was initiated in patients with MTAP-null previously treated advanced non-small cell lung cancer (NSCLC). In September, data were presented from a Phase 1 dose-escalation and initial dose-expansion study of AMG 193 in patients with MTAP-null solid tumors. The data demonstrated monotherapy activity and an acceptable safety profile. These data open opportunities to explore both monotherapy and combination therapy development strategies. Bemarituzumab Bemarituzumab is a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody. FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, is ongoing in patients with first-line gastric cancer. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in patients with first-line gastric cancer, has completed enrollment of the Phase 3 portion of the study. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab, continues to enroll patients in first-line gastric cancer. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy, is ongoing in patients with solid tumors with FGFR2b overexpression. Nplate The primary analysis of a Phase 3 study of Nplate as supportive care in chemotherapy-induced thrombocytopenia in gastrointestinal malignancies is complete. The Company continues to follow patients through a planned final analysis in H1 2025. Data presentation at a medical congress is anticipated in mid-2025. LUMAKRAS/LUMYKRAS CodeBreaK 202, a Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy, is enrolling patients with first-line KRAS G12C–mutated and programmed PD-L1 negative advanced NSCLC. Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 study of adults with previously treated locally advanced or metastatic KRAS G12C–mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing. The U.S Food and Drug Administration (FDA) extended the Prescription Drug User Fee Act (PDUFA) date for the Phase 3 CodeBreaK 300 study of LUMAKRAS plus Vectibix vs. investigator's choice of therapy in KRAS G12C–mutated metastatic colorectal cancer (CRC) from October 17, 2024, to January 17, 2025, to allow time for review of recently submitted supplemental data. CodeBreaK 301, a Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI, is enrolling patients with first-line KRAS G12C–mutated CRC. Inflammation TEZSPIRE The Company is planning to initiate Phase 3 studies in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) and a BEC ≥ 150 cells/µl or greater. Study initiation is anticipated in H1 2025. A Phase 3 study of TEZSPIRE is ongoing in patients with chronic rhinosinusitis with nasal polyps. Data readout is anticipated in H2 2024. A Phase 3 study of TEZSPIRE continues to enroll patients with eosinophilic esophagitis. In severe asthma, the WAYFINDER Phase 3b study and the PASSAGE Phase 4 real-world effectiveness study are fully enrolled. The SUNRISE Phase 3 study continues to enroll patients. Rocatinlimab (AMG 451/KHK4083) Rocatinlimab is a first-in-class T-cell rebalancing monoclonal antibody targeting the OX40 receptor. The eight study ROCKET Phase 3 program continues to enroll patients with moderate-to-severe atopic dermatitis (AD). To date, over 3,200 patients have been enrolled in the ROCKET program, with six studies having completed enrollment. In September, the Company reported results from the Phase 3 HORIZON study (part of the ROCKET program), evaluating rocatinlimab monotherapy vs. placebo in adults with moderate-to-severe AD. The study met its co-primary endpoints and all key secondary endpoints, achieving statistical significance versus placebo at week 24. 32.8% of patients in the rocatinlimab group achieved ≥ 75% reduction from baseline in Eczema Area and Severity Index score (EASI-75), compared to 13.7% placebo treated (19.1% difference, p<0.001). 19.3% of patients in the rocatinlimab group achieved a Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-ADTM) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 6.6% in placebo (12.8% difference, p<0.001). In the U.S., a more stringent scoring method was used (revised Investigator's Global Assessment, or rIGA) where 16.4% of patients in the rocatinlimab group achieved a score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline, compared to 4.9% in placebo (11.5% difference, p<0.001). Safety findings were consistent with those seen in the Phase 2b AD study. Additional key data readouts from the ROCKET Phase 3 program are expected in late 2024 through H2 2025: ROCKET SHUTTLE is a 24-week study evaluating rocatinlimab in combination with topical corticosteroids and/or topical calcineurin inhibitors in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET IGNITE is a 24-week study evaluating rocatinlimab monotherapy in adult patients with moderate-to-severe AD. Data readout is anticipated in late 2024 to early 2025. ROCKET ASCEND is a study evaluating rocatinlimab maintenance therapy in adult and adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. ROCKET ASTRO is a 52-week study evaluating rocatinlimab in adolescent patients with moderate-to-severe AD. Data readout is anticipated in H2 2025. A Phase 2 study of rocatinlimab is enrolling patients with moderate-to-severe asthma. A Phase 3 study of rocatinlimab is enrolling patients with prurigo nodularis. Otezla In September data were presented from: a Phase 3 study of Japanese patients with Palmoplantar Pustulosis (PPP) demonstrating maintained or increased efficacy (compared with the week 16 primary analysis) and no new safety signals with 52 weeks of Otezla treatment. the DISCREET moderate-to-severe genital psoriasis study demonstrating that improvements in disease severity, symptoms, and quality of life with Otezla treatment were maintained at week 32. No new safety signals were observed. the FOREMOST study of patients with oligoarticular psoriatic arthritis, where Otezla demonstrated sustained benefits in skin, joint, fatigue, and pain symptoms through 48-weeks. Blinatumomab Blinatumomab is a bispecific T-cell engager (BiTE) molecule targeting CD19. A Phase 2 study of blinatumomab was initiated in patients with autoimmune disease with an initial focus on systemic lupus erythematosus (SLE) with nephritis. Inebilizumab Inebilizumab is a monoclonal antibody targeting CD19. A Phase 2 study of inebilizumab was initiated in patients with autoimmune disease with an initial focus on SLE with nephritis. Efavaleukin alfa (AMG 592) Efavaleukin alfa is an interleukin 2 (IL 2) mutein Fc fusion protein. A Phase 2b study of efavaleukin alfa in patients with ulcerative colitis was terminated due to the study meeting a prespecified futility threshold, and not related to safety concerns. Ordesekimab (AMG 714/PRV-015) Ordesekimab is a monoclonal antibody that binds interleukin-15. A Phase 2b study of ordesekimab is ongoing in patients with nonresponsive celiac disease. AMG 104 (AZD8630) AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen-binding (Fab). A Phase 2 study was initiated in patients with asthma. Rare Disease TAVNEOS A Phase 3, open-label study of TAVNEOS in combination with Rituximab or a cyclophosphamide-containing regimen, is enrolling patients from 6 years to < 18 years of age with active ANCA-associated vasculitis (Granulomatosis with Polyangiitis (GPA) / Microscopic Polyangiitis (MPA)). TEPEZZA In September, TEPEZZA was approved for the treatment of active Thyroid Eye Disease (TED) by Japan's Ministry of Health, Labour and Welfare (MHLW). Regulatory review in multiple additional geographies continues. A Phase 3 study of TEPEZZA in Japan continues to enroll patients with chronic or low clinical activity score TED. A Phase 3 study evaluating the subcutaneous route of administration of teprotumumab is enrolling patients with TED. KRYSTEXXA Data from the AGILE study evaluating the safety, tolerability, and efficacy of KRYSTEXXA administered with a shorter infusion duration in patients with uncontrolled gout receiving methotrexate as co-administration will be presented at the American College of Rheumatology Convergence (ACR) in November. UPLIZNA The Company recently presented results of the Phase 3 MINT clinical study evaluating the efficacy and safety of UPLIZNA for the treatment of generalized myasthenia gravis (gMG). UPLIZNA demonstrated a clinically meaningful and statistically significant Myasthenia Gravis Activities of Daily Living (MG-ADL) score improvement after two doses compared to placebo at Week 26: -4.2 overall improvement, -1.9 placebo adjusted (p < 0.0001, primary endpoint). In the acetylcholine receptor autoantibody-positive (AChR+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -4.2 overall improvement, -1.8 placebo adjusted (p = 0.0015, secondary endpoint). In the muscle-specific kinase autoantibody-positive (MuSK+) population, UPLIZNA demonstrated a clinically meaningful and statistically significant MG-ADL score improvement compared to placebo at Week 26: -3.9 overall improvement, -2.2 placebo adjusted (p = 0.0297, secondary endpoint). UPLIZNA demonstrated a statistically significant Quantitative Myasthenia Gravis (QMG) score improvement after two doses compared to placebo at week 26: -4.8 overall improvement, -2.5 placebo adjusted (p = 0.0002, secondary endpoint). In the AChR+ population, UPLIZNA demonstrated a clinically meaningful and statistically significant QMG score improvement compared to placebo at week 26: -4.4 overall improvement, -2.5 placebo adjusted (p = 0.0011, secondary endpoint). In the MuSK+ population, the mean change from baseline in QMG score at Week 26 showed a trend favoring UPLIZNA but was not statistically significant (-5.2 for UPLIZNA and -3.0 for placebo, difference -2.3, p=0.1326). Patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. The overall safety results during the placebo-controlled period of the study were consistent with the known safety profile of UPLIZNA. 52-week data from the AChR+ cohort and from AChR+ and MuSK+ patients in the open-label period of the study will be presented at a future date. Planning for regulatory submissions for gMG is underway. In August, the FDA granted Breakthrough Therapy Designation for UPLIZNA in the treatment of Immunoglobulin G4-related diseases (IgG4-RD) based upon data from the Phase 3 MITIGATE study. Regulatory filing activities for IgG4-RD are underway. MITIGATE results will be presented at ACR in November. Dazodalibep Dazodalibep is a fusion protein that inhibits CD40L. Two Phase 3 studies of dazodalibep in Sjögren's disease are enrolling patients. The first study is in patients with moderate-to-severe systemic disease activity, and the second study is in patients with moderate-to-severe symptomatic burden and low systemic disease activity. Daxdilimab Daxdilimab is a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7). A Phase 2 study of daxdilimab is ongoing in patients with moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care. A Phase 2 study of daxdilimab is ongoing in patients with dermatomyositis and antisynthetase inflammatory myositis. Fipaxalparant Fipaxalparant is a lysophosphatidic acid receptor 1 (LPAR1) antagonist. A Phase 2 study of fipaxalparant in patients with idiopathic pulmonary fibrosis is complete. The study did not meet any of the primary or secondary endpoints. Development of fipaxalparant in this indication will be discontinued. A Phase 2 study of fipaxalparant has completed enrollment of patients with diffuse cutaneous systemic sclerosis. Biosimilars In August, the FDA approved PAVBLUTM (aflibercept-ayyh) (ABP 938), a biosimilar candidate to EYLEA® (aflibercept), for the treatment of retinal conditions, including neovascular age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy. A randomized, double-blind pharmacokinetic similarity study of ABP 206 compared with OPDIVO® (nivolumab) is enrolling patients with resected stage III or stage IV melanoma in the adjuvant setting. A randomized, double-blind comparative clinical study of ABP 206 compared with OPDIVO is enrolling patients with treatment-naïve unresectable or metastatic melanoma. A randomized, double-blind combined pharmacokinetic/comparative clinical study of ABP 234 compared to KEYTRUDA® (pembrolizumab) is enrolling patients with advanced or metastatic non-squamous non-small cell lung cancer. TEZSPIRE is being developed in collaboration with AstraZeneca. AMG 104 is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin. Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck & Co., Inc. Non-GAAP Financial Measures In this news release, management has presented its operating results for the third quarters of 2024 and 2023, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2024 and 2023. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.  Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. 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Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. 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We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. 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CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

iStock, wildpixel Alto Neuroscience’s depression treatment failed to beat placebo just nine months after the biotech went public. The stunning failure called to mind Acelyrin, which faced a similar fate last year. Alto Neuroscience’s Phase IIb therapy has failed to improve symptoms of major depressive disorder compared to placebo, sending the biotech’s shares down 60% in after-market trading Tuesday evening. The clinical failure comes nine months after Alto became one of the earliest biotechs of 2024 to IPO , raising $128.6 million in early February. The stunning failure of ALTO-100 brings back echoes of Acelyrin last year; it was one of the few biotechs to test the IPO waters in 2023, raising a massive $540 million, only to fail a clinical trial a few months later. Alto revealed the failure in an after-market release Tuesday evening. ALTO-100 did not beat placebo in the Phase IIb trial of patients with MDD, however safety and tolerability were as expected. Alto will now conduct a full analysis of the data set to determine next steps. “We are disheartened by the results from this study as the unmet need in this patient population is immense,” said Alto CEO Amit Etkin in a statement. William Blair analysts called the results “a clear miss” for Alto, pointing out that the study was well conducted and the placebo performed according to historical precedent. Stifel similarly said the drug “simply didn’t succeed.” “The press release is light on data details but quite firm in that the trial was a failure, and there (commendably) isn’t any data dredging or overreaching post-hoc analyses in an attempt to salvage the asset,” Stifel noted in a note Tuesday evening. Platform in Question The treatment was developed with Alto’s precision psychiatry platform, which has been touted as a way to develop highly personalized and effective psychiatry therapies. Analysts from Jefferies, William Blair and Stifel wondered what the read-through would be for Alto’s deeper portfolio of neuropsychiatry treatments. “The clear top-line miss of ALTO-100 in MDD undoubtedly will cast investor doubt on Alto’s Precision Neuropsychiatry approach to pair specific mechanisms of action to patient biomarkers of drug response,” William Blair’s team wrote. Alto used a memory-based biomarker to sort patients before randomizing them into treatment and placebo arms. The main endpoint was a rating on the standard Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo at the end of the six-week treatment period. The study was conducted in the U.S. with 301 adults. Patients who were in the biomarker-defined group did not demonstrate a statistically significant improvement in depression symptoms compared to placebo. The treatment also did not spur improvement on other pre-specified key secondary endpoints. “While the results are surprising and disappointing, I am proud of our team for conducting a first-of-its-kind precision biomarker-based study in psychiatry. We will move quickly to evaluate the full data set to better understand these findings and incorporate learnings from this large data set across our platform,” Etkin said. ALTO-100 is also being studied in a Phase IIb trial of patients with bipolar disorder. While Alto was taking an innovative approach, William Blair contends the biotech took on one of the toughest challenges: depression itself. “While today’s data points draw increased scrutiny on the biomarker stratification approach, historically placebo-controlled MDD studies have been high-risk, and this one appears no different,” the firm wrote. Sage Therapeutics is one recent example. While the company achieved FDA clearance for Zurzuvae in postpartum depression, the drug was not cleared in MDD because the FDA found the company had failed to provide “substantial evidence of effectiveness” to support approval. Investors will now shift focus to Alto’s next pipeline asset, ALTO-300, which is also in development for MDD with a readout expected in the first half of 2025. The drug, also known as agomelatine, is approved in Europe and Australia for depression. Alto has already completed a Phase IIa study verifying the EEG-based biomarker to be used. William Blair analysts suggested this asset is slightly more de-risked than ALTO-100, given its existing approvals elsewhere in the world. “We still think the Alto precision psych approach has merit, and we do note that all drugs within the pipeline operate by fundamentally different mechanisms-of-action,” Stifel analysts wrote. “In our view, better patient selection, and ‘homogenizing’ trial populations, is still a winning strategy in CNS, and for this reason we do think Alto’s other shots-on-goal for fundamentally different assets should not be written off.” Alto has plenty of cash to operate on despite the failure, Etkin said in the release. The company reported $193.6 million as of June 30 , which will extend its cash runway into 2027 through multiple upcoming readouts. Besides the ALTO-300 readout next year, the company is also expecting one for ALTO-203, also in MDD. Echoes of 2023 Alto’s failure calls to mind a similar stumble last year from Acelyrin, which raised a massive $540 million in an IPO to fuel its immunology aspirations. But just months later, it reported that lead asset izokibep had failed in a Phase IIb/III trial in patients with hidradenitis suppurativa. Acelyrin’s shares tumbled by more than half and sent a chill through the markets that had already been lukewarm to biotech public debuts. Alto’s shares fell 60% to $5.70 in after-market trading Tuesday evening, compared to $14.53 at close just hours before. The company’s shares began trading on February 2 at $22 apiece. Just like Alto, Acelyrin had another arrow in its quiver with izokibep, which later met the primary endpoint of a Phase IIb/III psoriatic arthritis trial. The therapy was also retested in hidradenitis suppurativa, meeting the main goal of a Phase III trial, the company reported in August. Despite the success, Acelyrin has suspended investment in both indications for izokibep and will focus on thyroid eye disease therapy lonigutamab.