Acute myocardial infarction

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. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. 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. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. 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. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. 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

Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland – October 29, 2024 Idorsia Ltd (SIX: IDIA) today announced its financial results for the first nine months of 2024. Highlights Net revenue 9M 2024 at CHF 53 million.US GAAP operating loss 9M 2024 of CHF 154 million and Non-GAAP operating loss of CHF 248 million.Improved Guidance for 2024, driven by diligent cost control.QUVIVIQ™ (daridorexant) total net sales of CHF 39 million in 9M 2024.Commercial partnership for QUVIVIQ with Menarini France.QUVIVIQ approved for the treatment of insomnia in Japan.TRYVIO™ (aprocitentan) commercially available in the US since October 2024.JERAYGO™ (aprocitentan) approved by the European Commission in June 2024 and marketing authorization applications submitted in the UK, Canada, and Switzerland.Collaboration with Neurocrine Biosciences comes to an end. André C. Muller, Chief Executive Officer of Idorsia, commented:“The one thing everyone wants to hear about – both internally and externally – is the status of a deal with aprocitentan. I’m pleased to share that our efforts on this front are advancing well. Our improved financial guidance includes our cost-conscious attitude across the whole organization, without compromising advancements, such as making progress in ramping up sales of QUVIVIQ, making TRYVIO available in the US, and expanding marketing authorization for JERAYGO.” Financial results US GAAP resultsNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(211)(275)(118)150Operating income (loss)(154)(144)(90)231Net income (loss)(180)(181)(101)224Basic EPS(1.00)(1.02)(0.55)1.26Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.00)(1.02)(0.55)0.96Diluted weighted average number of shares180.5178.2182.4232.5 Net revenue of CHF 53 million in the first nine months of 2024 is the result of QUVIVIQ product sales (CHF 39 million), product sales to partners in the Asia-Pacific-Region (CHF 9 million) and contract revenue recognized in connection with Owkin (CHF 3 million). This compares to CHF 131 million in the first nine months of 2023, which included CHF 34 million sales of PIVLAZ in Japan (assigned in the meantime to Nxera Pharma as part of a transaction, more details can be found in the dedicated press release) and CHF 68 million one-off impact of the Nxera deal as well as CHF 4 million revenue share from Johnson & Johnson related to ponesimod sales (revenue-sharing agreement now eliminated as part of the reacquisition of aprocitentan, more details can be found in the dedicated press release). US GAAP operating expenses in the first nine months of 2024 benefited from extraordinary income of CHF 125 million from the Viatris deal resulting in an expense of CHF 211 million (CHF 275 million in the first nine months of 2023), of which CHF 16 million related to cost of sales (CHF 7 million in the first nine months of 2023), CHF 111 million to R&D expenses (CHF 235 million in the first nine months of 2023), and CHF 209 million to SG&A expenses (CHF 318 million in the first nine months of 2023). US GAAP net loss in the first nine months of 2024 amounted to CHF 180 million (CHF 181 million net loss in the first nine months of 2023). The net loss was favorably impacted by a one-off income related to the Viatris deal of CHF 125 million (CHF 302 million one-off income related to the Nxera deal in the first nine months of 2023) and lower operating expenses throughout all functions. The US GAAP net loss resulted in a basic net loss per share of CHF 1.00 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 1.02 (basic and diluted) in the first nine months of 2023. Non-GAAP* measuresNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(305)(517)(106)(124)Operating income (loss)(248)(386)(78)(44)Net income (loss)(258)(420)(75)(51)Basic EPS(1.43)(2.36)(0.41)(0.29)Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.43)(2.36)(0.41)(0.29)Diluted weighted average number of shares180.5178.2182.4178.4 * Idorsia measures, reports, and issues guidance on non-GAAP operating performance. Idorsia believes that these non-GAAP financial measurements more accurately reflect the underlying business performance and therefore provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance. Non-GAAP net loss in the first nine months of 2024 amounted to CHF 258 million: the CHF 78 million difference versus US GAAP net loss was mainly due to the one-off effect of the Viatris deal (CHF 125 million income), depreciation and amortization (CHF 14 million), share-based compensation (CHF 17 million) and a consent fee paid in shares to the bondholders resulting from amended terms of the 2024 convertible bonds (CHF 14 million). The non-GAAP net loss resulted in a net loss per share of CHF 1.43 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 2.36 (basic and diluted) in the first nine months of 2023. Viatris collaborationIn March 2024, Idorsia closed agreements with Viatris Inc. (NASDAQ: VTRS), a global healthcare company, for collaboration on the global development and commercialization of two Phase 3 assets – selatogrel and cenerimod – with Idorsia receiving an upfront payment of USD 350 million, and the right to potential development and regulatory milestone payments of up to USD 300 million, potential sales milestone payments of up to USD 2.1 billion, and potential contingent tiered royalties from mid-single- to low-double-digit percentage on annual net sales. A joint development committee is overseeing the development of the ongoing Phase 3 programs for selatogrel and cenerimod up to regulatory approval. Idorsia will contribute up to USD 200 million in the next 3 years and transferred the dedicated personnel for both programs to Viatris. Viatris has worldwide commercialization rights for both selatogrel and cenerimod (excluding, for cenerimod only, Japan, South Korea, and certain countries in the Asia-Pacific region). Idorsia has also granted Viatris a right of first refusal and first negotiation for certain other pipeline assets. Convertible bonds 2024In July 2018, the Group issued CHF 200 million of senior unsecured convertible bonds (ISIN: CH0426820350), which were due to mature on July 17, 2024. On May 6, 2024, a bondholder meeting was held, where 83.5% of the total outstanding bondholders voted in favor of amendments to the terms of the bonds. The approved bond terms include an amended conversion price of CHF 6.00, extended maturity date of January 17, 2025, and the option to call the bonds at par, in full or in part, at any time upon giving ten trading days' notice. A consent fee of 8,000 shares per Bond was paid to bondholders on September 5, 2024. Financial outlook 2024For 2024 – excluding unforeseen events – the company expects QUVIVIQ net sales of around CHF 55 million; SG&A expenses of around CHF 265 million; R&D expense of around CHF 130 million for Idorsia-led pipeline assets; non-GAAP operating expenses around CHF 400 million. This performance would result in a non-GAAP operating loss of around CHF 350 million (excluding contract revenues and the one-off benefit from the Viatris deal). The company expects US GAAP operating loss for 2024 to reach CHF 260 million which includes a one-off benefit of CHF 125 million from the Viatris deal. Arno Groenewoud, Chief Financial Officer, commented:“While closing a deal for TRYVIO is a key focal point, we have also sharpened our cost-conscious approach, which we will increase going forward. Hence, we have been able to stretch the cash runway out to about year-end 2024, which allows us to appropriately plan and execute the next steps of our financial strategy. Furthermore, as a result of lower than expected spending we can upgrade our US GAAP and non-GAAP operating loss guidance by around 60 million Swiss francs each, taking them to 260 million and 350 million Swiss francs, respectively.” Liquidity and indebtednessAt the end of the first nine months of 2024, Idorsia’s liquidity amounted to CHF 92 million. (in CHF millions)Sep 30, 2024Jun 30, 2024Dec 31, 2023Liquidity Cash and cash equivalents92237145Total liquidity*92237145 Indebtedness Convertible loan335335335Convertible bond797797796Other financial debt162162162Total indebtedness1,2941,2941,293 *rounding differences may occur Commercial operationsIn the first nine months of 2024, QUVIVIQ™ (daridorexant) in the US, Germany, Italy, Switzerland, Spain, UK, Canada, Austria, and France generated total product sales of CHF 39 million. United States ProductMechanism of actionIndicationCommercially available sinceDual orexin receptor antagonistTreatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceMay 2022 In the US, net sales of QUVIVIQ® (daridorexant) in the first nine months of 2024 reached CHF 21 million, an increase of +41% versus the first nine months of 2023. As of the end of the third quarter 2024, more than 165,000 patients have been treated with QUVIVIQ since launch in the US, over 500,000 prescriptions have been dispensed, and the product has been prescribed by almost 50,000 healthcare professionals. Tosh Butt, President, and General Manager of Idorsia US, commented:“Due to budget constraints we have recently reduced our field force for QUVIVIQ. Despite the reduction, the sales are holding-up for now. Importantly, the citizen petition requesting a review of the evidence from available data, which will hopefully lead to the descheduling of the DORA class of chronic insomnia medications, continues to make progress.” For more information about QUVIVIQ in the US, see the Full Prescribing Information (PI and Medication Guide). ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugsOctober 2024 On March 19, 2024, the US Food and Drug Administration (FDA) approved TRYVIO™ (aprocitentan) for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. Tosh Butt concluded:“Idorsia is making robust progress with the preparation of everything required for a full commercial launch of TRYVIO by the end of the first quarter of 2025. Both the REMS program and specialty distribution channel are fully up and running, we have begun engaging with hypertension experts through our presence at major cardiovascular and nephrology congresses. The initial discussions with payors are also encouraging. TRYVIO is now available to prescribe to the millions of patients in the US whose high blood pressure is not adequately controlled by other drugs. We have everything in place except a field-force and funding for promotional activities, which is dependent on a partnership deal.” Further details on the approval, together with commentary from company management can be found in the dedicated press release and investor webcast available from the company corporate website. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). Europe and Canada ProductMechanism of actionIndicationCommercially availableDual orexin receptor antagonistTreatment of adult patients with insomnia characterised by symptoms present for at least three months and considerable impact on daytime functioningSweden: Sept. 2024France: Mar. 2024Austria: Feb. 2024UK: Oct. 2023Spain: Sept. 2023Switzerland: Jun. 2023Germany: Nov. 2022Italy: Nov. 2022 Management of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceCanada: Nov. 2023 QUVIVIQ (daridorexant) net sales in the first nine months of 2024 reached CHF 18 million in the EUCAN region. In the third quarter of 2024, net sales have increased by 46% compared to the second quarter of 2024. In Germany, QUVIVIQ was launched in November 2022. By law, sleep medications were then subject to a 4-week prescribing limitation (Anlage III BtMG). Following a review by the Federal Joint Committee (G-BA) this limitation was lifted for QUVIVIQ in November 2023. This makes it the only sleep medication in Germany that can be prescribed for long-term treatment of chronic insomnia. In December 2023, the price negotiated for QUVIVIQ under the AMNOG process became effective. Following the lifting of the prescribing limitation, the company submitted a second AMNOG dossier for the long-term treatment of chronic insomnia disorder (beyond 4 weeks), reflecting the indication approved by the EMA in 2022. The second AMNOG process is expected to end in March 2025. The progress made in Germany is reflected by the performance of QUVIVIQ on the market, with sales doubling in the first nine months of 2024 compared to the first nine months of 2023. In Italy, QUVIVIQ was launched in November 2022. Currently, QUVIVIQ can only be prescribed by neurologists, psychiatrists, and specialists from sleep centers, and no sleep therapy is reimbursed. The company submitted a reimbursement dossier in June 2023 and requested the expansion of the prescriber base. The submission – detailing the efficacy and safety profile of QUVIVIQ and its estimated budget impact and cost-effectiveness in Italy – is under review, with a hearing expected to take place before the end of the year. In Switzerland, QUVIVIQ was launched to the self-pay market in June 2023. Following the launch of QUVIVIQ, awareness and sales have increased solidly. Reimbursement discussions are ongoing and remain a priority for Switzerland. In Spain, QUVIVIQ was launched to the self-pay market in September 2023. Spain represents the largest insomnia market in Europe, as was apparent in the first months of this product’s availability, despite it only being launched to the self-pay market. The company submitted a reimbursement dossier to the Spanish authorities in July 2024, in order to allow equal access for all patients with chronic insomnia. In the UK, QUVIVIQ is recommended as first-line pharmaceutical treatment for patients with chronic insomnia, after, or as an alternative to, cognitive behavioral therapy for insomnia (CBT-I). QUVIVIQ was launched in October 2023 and the team has achieved full reimbursement throughout the UK. The priority in the UK is to secure regional access, which currently stands at around 80%, as well as raising awareness of QUVIVIQ among general practitioners. In Austria, QUVIVIQ was made available in February 2024. A reimbursement dossier was submitted in October 2024, with a conclusion expected in the second half of 2025. In France, QUVIVIQ was included in both the hospital and the retail formulary list of reimbursed pharmaceutical specialties in January 2024 and launched in March 2024 as the first and only pharmacotherapy recommended for the treatment of chronic insomnia disorder. There was a very strong uptake at launch largely due to the excellent market preparation work with psychiatrists. This can be seen by the fact that the majority of prescriptions are being made by the specialists, despite the French market being composed of 55’000 general practitioners who between them represent 75% of the insomnia prescriptions. As a result, the priority becomes expanding awareness to the primary care market to secure strong long-term growth. To address this, Idorsia is expanding its commercial reach from specialist prescribers to general practitioners (GPs) through a new commercial partnership with Menarini in France. In Sweden, QUVIVIQ was made available in September 2024. A reimbursement dossier was submitted in May 2024. As a result, a decision on reimbursement is expected by the end of 2024. In Canada, after being approved in April 2023, QUVIVIQ was launched in November 2023 to the private market, representing 55% of the Canadian insomnia market. The reimbursement dossier was submitted to private market payers in the third quarter of 2023 and currently stands at 80% coverage. The focus is now on public payers with the submission confirmation in Quebec received in October 2024 and submissions in all other provinces ongoing and to be completed by year end. Benjamin Limal, President of Europe and Canada region, commented:“Securing public access to Europe’s only dual orexin receptor antagonist remains our number one priority throughout the EUCAN region – this is the pathway to unlocking the true value of QUVIVIQ. Until then, the performance is satisfactory with a great adoption from specialists and a strong quarterly growth in demand and sales. As one of the newest launches, I have to mention France – QUVIVIQ is really off to a flying start and we are quickly reinforcing the launch momentum through a commercial partnership with Menarini, experts with established relationships in primary care, to handle the promotion of QUVIVIQ to GPs.” For more information about QUVIVIQ in the EU, see the Summary of Product Characteristics. For more information about QUVIVIQ in Switzerland, see the Patient Information and Information for Healthcare Professionals. For more information on the marketing authorization of QUVIVIQ in Canada, see the Product Monograph. ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal productsApproved Jun. 2024 On June 27, 2024, the European Commission (EC) approved JERAYGO™ (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control. Further details on the approval, together with commentary from company management can be found in the dedicated press release available from the company corporate website. For more information about JERAYGO in the EU, see the Summary of Product Characteristics. Research & DevelopmentIdorsia has a diversified and balanced portfolio, comprising assets developed and/or marketed by Idorsia and assets that are partner-led to maximize the value we have created. Our drug discovery engine has produced innovative drugs with the potential to transform the treatment paradigm in multiple therapeutic areas, including CNS, cardiovascular, and immunological disorders, as well as orphan diseases. The company also has a vaccine platform for the discovery and development of glycoconjugate vaccines containing synthetic antigenic glycan molecules, with or without a carrier protein, to prevent infection. Idorsia-led portfolio CompoundMechanism of actionTarget indicationStatusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaCommercially available in the US, Germany, Italy, Switzerland, Spain, the UK, Canada, Austria, France, and Sweden; approved throughout the EUTRYVIO™ (aprocitentan) Dual endothelin receptor antagonistSystemic hypertension in combination with other antihypertensivesCommercially available in the USJERAYGO™ (aprocitentan)Dual endothelin receptor antagonistResistant hypertension in combination with other antihypertensivesApproved in the EU; Marketing authorization applications submitted in the UK, Canada, and SwitzerlandLucerastatGlucosylceramide synthase inhibitorFabry diseasePhase 3 primary endpoint not met; open-label extension study ongoingPhase 3 focused on renal function in preparationDaridorexantDual orexin receptor antagonistPediatric insomniaPhase 2 in pediatric insomnia ongoingACT-1004-1239ACKR3/CXCR7 antagonistDemyelinating diseases including multiple sclerosis Phase 2 in preparationACT-777991CXCR3 antagonistVitiligoPhase 2 in preparationSinbaglustatGBA2/GCS inhibitorRare lysosomal storage disordersPhase 1 completeIDOR-1117-2520UndisclosedImmune-mediated disordersPhase 1 ongoingIDOR-1134-2831Synthetic glycan vaccineClostridium difficile infectionPhase 1 ongoing Further details including the current status of each project in our portfolio can be found in our innovation fact sheet. Idorsia partner-led portfolioFor Idorsia, sophisticated partnerships are a way of gaining strategic access to technologies or products and fully exploiting our discovery engine and clinical pipeline. We seek suitable external project partners to maximize the value of internal innovation. CompoundMechanism of actionTarget indicationPartner/statusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaSimcere: Approved for the treatment of insomnia in Hong-KongQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaNxera Pharma: license to develop and commercialize for Asia-Pacific region (excluding China)Approved for the treatment of insomnia in JapanDaridorexantDual orexin receptor antagonistInsomniaSimcere: license to develop and commercialize for Greater China regionNDA submitted in Greater ChinaSelatogrelP2Y12 inhibitorAcute myocardial infarctionViatris: worldwide development and commercialization rightsPhase 3 “SOS-AMI” program ongoingCenerimodS1P1 receptor modulatorSystemic lupus erythematosusViatris: worldwide development and commercialization rights (excluding Japan, South Korea, and certain countries in the Asia-Pacific region)Phase 3 “OPUS” program ongoingDaridorexantDual orexin receptor antagonistPosttraumatic stress disorder (PTSD)US Department of Defense (DOD): Idorsia is supporting a clinical study sponsored by the US DOD to develop new therapies to treat PTSDACT-1002-4391EP2/EP4 receptor antagonistImmuno-oncologyOwkin: global license to develop and commercializePhase 1 in preparation On October 1, 2024, Nxera Pharma announced that it had entered a commercial partnership agreement with Shionogi & Co., Ltd regarding the distribution and sales for QUVIVIQ in Japan. At the same time, the previous commercialization agreement between Nxera and Mochida Pharmaceutical Co., Ltd. was terminated. After negotiation among Nxera, Shionogi and Mochida regarding the optimal sales scheme, Shionogi is solely responsible for distribution and sales activities in Japan. Idorsia and Neurocrine Biosciences had a collaboration for ACT-709478, Idorsia’s novel T-type calcium channel blocker. The compound was investigated as a treatment of pediatric patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSCW), a rare form of pediatric epilepsy. The Phase 2 study did not meet the primary endpoint in June 2022, and further analysis from an open-label extension study resulted in the decision to stop further development. As a result, the development agreement has come to an end. Further details including the current status of each project in our partner-led portfolio can be found in our innovation fact sheet. Results Day CenterInvestor community: To make your job easier, we provide all relevant documentation via the Results Day Center on our corporate website: www.idorsia.com/results-day-center. Upcoming Financial Updates Full Year 2024 Financial Reporting together with the publication of the Annual Report 2024 on February 27, 2025 Notes to the editor About IdorsiaIdorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development, and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 25-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 750 highly qualified specialists dedicated to realizing our ambitious targets. For further information, please contactAndrew C. WeissSenior Vice President, Head of Investor Relations & Corporate CommunicationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com media.relations@idorsia.com www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

尿激酶原是一种基因工程制备的药物，也是一种新型的特异性溶栓药物。其结构为单肽链，具有较长的半衰期，可持续发挥溶栓作用。在血管内无血栓存在时，尿激酶原具有有限的酶活性，但在与血栓接触后，血栓纤维蛋白部分溶解，使纤维蛋白E片段暴露，从而增强了尿激酶原的酶活性，使其将纤溶蛋白酶原转化为纤溶蛋白的活性增加500倍以上。在这种情况下，尿激酶原可直接作用于纤溶酶原，尤其是与C端两个赖氨酸残基结合的纤溶酶原，进一步增强了尿激酶原的活性。 尿激酶原主要用于治疗血栓引发的急性心肌梗死（acute myocardial infarction，AMI）、肺栓塞、脑卒中等疾病，因其溶栓能力强、血管再通率高、出血风险小等特点而备受青睐。 重组人尿激酶原在临床中应用广泛 重组人尿激酶原在急性心肌梗死治疗中的应用 AMI的危险性主要为心肌缺血引起的心肌细胞坏死，可能导致心脏功能受损、心力衰竭、心律失常以及患者死亡。AMI还可能引发并发症，如心包炎、心律失常、心源性休克等，严重影响患者的生命质量和预后。 《欧洲心脏病学会关于ST段抬高患者急性心肌梗死管理指南》指出，早期对ST段抬高型心肌梗死（ST-segment elevation myocardial infarction，STEMI）进行再灌注疗法，可以显著促进患者康复，降低死亡风险。此类疗法主要采用经皮冠状动脉介入治疗（percutaneous coronary intervention，PCI）和药物溶栓两种方式。PCI是目前冠状动脉再灌注的首选方法，它通过支架置入和球囊扩张等手段迅速打通狭窄或闭塞的冠状动脉，恢复血流。然而，部分患者在手术后可能出现微血栓形成或微循环障碍，出现冠状动脉无复流或慢血流情况。在条件有限的地区，由于缺乏成套的医疗设备和专业技术人员，单纯静脉溶栓疗依旧是恢复心肌再灌注的首选方案。有研究显示，如果从AMI急性发作到实施PCI的时间超过两小时，PCI的效果将大打折扣，冠状动脉再开通率将低于单纯溶栓治疗。有专家认为，静脉溶栓和PCI联合的治疗方法，既能克服治疗延迟的问题，又能提高血管开通的成功率，展现出较好的治疗前景。 以上研究显示，尿激酶原在治疗AMI上效果更佳，能更有效地恢复心脏血流灌注、降低心脏受损标志物指标，保持血浆中的纤溶平衡，且只对血栓形成部位产生作用，对人体正常部位产生影响较小，有着更广泛的适用性和更高的安全性，出血等不良事件发生概率显著降低。在PCI手术中联合使用尿激酶原溶栓的初期治疗效果优于仅采用PCI或静脉溶栓的方式。 重组人尿激酶原在脑梗死治疗中的应用 脑梗死通常因患者动脉粥样硬化引起脑血管狭窄，导致血流缓慢、局部血供下降和血栓形成，终末期形成脑梗死。治疗方法主要包括脑血管介入和溶栓两种方式。介入治疗虽然能迅速救治患者，但其对高端设备和专业团队的需求限制了其在部分医疗机构的应用。静脉溶栓作为首选策略，能在患者脑梗死初期有效恢复受损脑区功能，减少中枢神经损伤，提升预后。目前，阿普替酶和尿激酶是溶栓治疗中主要使用的药物。在脑梗死发作后的可溶栓时间窗内进行静脉溶栓，可以最大程度地恢复梗塞灶周围半暗带脑细胞的功能，从而降低中枢神经系统的损伤程度，提高患者的预期恢复程度。 关于尿激酶原溶栓治疗老年急性脑梗死的临床疗效及对神经功能和生活质量的影响的有关研究显示，治疗方案分为高剂量组（尿激酶原50mg）、低剂量组（尿激酶原35mg）和对照组（阿替普酶），每组各40例，检测3组患者治疗前及溶栓后血流动力学、神经功能相关因子、神经功能及生活质量评分情况。与对照组相比，高、低剂量组血流动力学指标均升高（P<0.05），神经功能因子显著降低（P<0.05）。治疗3个月后，高、低剂量组Barthel指数、SF-36评分均比对照组明显升高（P<0.05），且低剂量组可维持更好的治疗效果。该研究显示，尿激酶原对于提升患者神经功能受损的状况具有显著效果，其安全性和有效性表现出色，因而推荐在临床上广泛应用。 重组人尿激酶原在静脉血栓栓塞症治疗中的应用 静脉血栓栓塞症主要包括肺血栓栓塞症和深静脉血栓形成（deep venous thrombosis，DVT）这两种形式。DVT通常发生在下肢，症状包括患侧肢体红疹、间歇性或持续性肿胀、皮肤温度上升，可能伴随疼痛。DVT的血凝块如果移动至肺部，可能引起肺动脉栓塞，表现为难以缓解的低氧血症、呼吸困难、胸痛、心率加快及血压下降，严重时可危及患者生命。还有研究显示，急性髂股静脉血栓的首选治疗方法是导管溶栓与抗凝治疗相结合，可以有效地促进血栓溶解，防止其进一步形成和扩散，帮助患者恢复健康；连续应用20mg小剂量尿激酶原治疗67名急性肺栓塞患者，能够明显改善患者临床症状，提高治愈率，且不增加出血风险。 尿激酶原具有的高效性与安全性为治疗高危急性肺栓塞提供了更优秀的治疗方法，值得临床推广应用。 重组人尿激酶原在急性下肢动脉血栓治疗中的应用 下肢动脉血液的流速较快、压力较大，一般情况下并不容易形成血栓。然而，一旦出现动脉血管内皮受损、血液高凝状态、动脉管腔狭窄等情况，血栓形成的风险就会大大增加。目前，对于该病常采用的治疗方式包括置管溶栓、动脉切开取栓和经皮血管腔内机械血栓清除等，并辅以抗凝治疗，已经在临床取得了较为满意的效果。有研究比较了尿激酶原和尿激酶在急性下肢动脉血栓治疗中的效果，结果显示，与尿激酶组相比，尿激酶原组在影像学改变和临床症状改善方面表现出更好的治疗效果。需要注意的是，该试验并未进行远期通畅率的随访，对患者的长期影响并无明确结论。因此，尿激酶原在急性下肢动脉血栓治疗中的有效性仍需要更多的证据来进一步确认，同样也说明对于研究尿激酶原在下肢动脉血栓中的应用有着广泛的思路。 重组人尿激酶原在新兴领域的应用前景 成熟药涂支架对重组人尿激酶原应用的启发 利用生物可降解聚合物制备药物释放系统是当前化学技术中最有前景的研究领域之一。在医疗器械上应用药物制剂控释，特别是在支架或药物球囊上涂层，可以提高临床治疗效果。 大量试验证实了尿激酶原的药理作用，其在溶解血栓性疾病的应用中表现出良好的效果。临床上广泛认可其安全性和高效性，在许多病例的治疗中作为首选药物。然而，对于临床应用尿激酶原还需进一步优化剂量选择和溶栓时间，尿激酶原的规范化使用指南还需要通过多中心、大样本研究来确立。此外，尿激酶原在新领域的应用，如药物涂层支架、超声介导的载药溶栓系统等可能是未来尿激酶原研究的重点领域之一。 来源：健康报 投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦