Granulomatosis With Polyangiitis

Strong balance sheet with successful completion of upsized $179.0 million initial public offering Treatment initiated in the first patient in an investigator-initiated basket trial of AlloNK® exploring multiple autoimmune indicationsTreated first patient in Artiva sponsored Phase 1/1b trial in patients with class III or IV lupus nephritis (LN) and expanded trial to include patients with systemic lupus erythematosus (SLE) without kidney involvement SAN DIEGO, Aug. 29, 2024 (GLOBE NEWSWIRE) -- Artiva Biotherapeutics, Inc. (Nasdaq: ARTV), a clinical-stage biotechnology company whose mission is to develop effective, safe, and accessible cell therapies for patients with devastating autoimmune diseases and cancers, today announced financial results for the second quarter ended June 30, 2024, and highlighted recent progress. “Artiva is at an inflection point as we advance AlloNK® in clinical development across multiple autoimmune indications and transition to a publicly traded company,” said Fred Aslan, M.D., Artiva’s Chief Executive Officer. “With two trials in autoimmunity underway, we are focused on the potential of AlloNK® in delivering effective, safe, and accessible cell therapies for patients with devastating autoimmune disease.” Recent Business Highlights AlloNK® Treatment initiated in the first patient in an investigator-initiated basket trial (IIT) exploring AlloNK® in combination with rituximab in patients with rheumatoid arthritis, pemphigus vulgaris, granulomatosis with polyangiitis/microscopic polyangiitis, and SLE. The trial is being conducted by Integral Rheumatology & Immunology Specialists (IRIS), a community rheumatology clinic, demonstrating the potential to bring AlloNK® to patients in a community setting in addition to academic and transplant centers. The study is assessing the safety, tolerability, and clinical activity of AlloNK® (also known as AB-101). Announced treatment of the first LN patient in Artiva sponsored Phase 1/1b trial in April 2024. To Artiva's knowledge, this marks the first patient to receive an allogeneic, off-the-shelf NK cell therapy in a U.S. clinical trial for treatment of an autoimmune disease. In the Phase 1/1b trial, AlloNK® will be administered in combination with rituximab or obinutuzumab. The trial was expanded to include patients with SLE without kidney involvement.Expect to report initial data on autoimmune indications from at least one of the Phase 1/1b trial or the basket IIT in the first half of 2025. Corporate and Financial Updates Significantly extended cash runway through the completion of Artiva’s initial public offering (IPO). Strengthened balance sheet with approximately $179.0 million in gross proceeds from the IPO in July 2024, which extends cash runway at least through the end of 2026 and through key clinical data milestones. Second Quarter 2024 Financial Results Cash, Cash Equivalents and Short-Term Investments. As of June 30, 2024, Artiva had cash, cash equivalents, and short-term investments of $46.6 million. In addition, Artiva completed its IPO in July 2024 in which it sold 14,920,000 shares of its common stock, including partial exercise of the overallotment option, for gross proceeds of $179.0 million. Collaboration Revenue. Collaboration revenue was $0 for the three months ended June 30, 2024, compared to $3.5 million for the three months ended June 30, 2023. Revenues in 2023 were related to the Merck Sharpe & Dohme Corp. collaboration which was terminated in October 2023. Research and Development Expenses. Research and development expenses were $12.3 million for the three months ended June 30, 2024, compared to $11.3 million for the three months ended June 30, 2023. General and Administrative Expenses. General and administrative expenses were $3.9 million for the three months ended June 30, 2024, compared to $4.1 million for the three months ended June 30, 2023.Other Income (Expense), net. Other expense, net, was $1.7 million for the three months ended June 30, 2024, compared to other income, net, of $0.5 million for the three months ended June 30, 2023. Other expense, net, for the three months ended June 30, 2024, includes a loss on change in fair value of simple agreements for future equity (SAFEs) of $2.4 million. Net Loss. Net loss totaled $17.8 million for the three months ending June 30, 2024, as compared to $11.3 million for the three months ending June 30, 2023, with non-cash stock-based compensation expense of $1.5 million and $2.5 million for the three months ended June 30, 2024 and 2023, respectively. About Artiva Biotherapeutics Artiva is a clinical-stage biotechnology company whose mission is to develop effective, safe and accessible cell therapies for patients with devastating autoimmune diseases and cancers. Artiva’s lead program, AlloNK®, is an allogeneic, off-the-shelf, non-genetically modified, cryopreserved NK cell therapy candidate designed to enhance the antibody-dependent cellular cytotoxicity effect of monoclonal antibodies to drive B-cell depletion. AlloNK® is currently in clinical trials for treatment of systemic lupus erythematosus, for patients with or without lupus nephritis, and in an investigator-initiated basket trial in multiple autoimmune indications. Artiva’s pipeline also includes CAR-NK candidates targeting both solid and hematologic cancers. Artiva was founded in 2019 as a spin out of GC Cell, formerly GC Lab Cell Corporation, a leading healthcare company in the Republic of Korea, pursuant to a strategic partnership granting Artiva exclusive worldwide rights (excluding Asia, Australia and New Zealand) to GC Cell’s NK cell manufacturing technology and programs. Artiva is headquartered in San Diego, California. For more information, please visit https://www.artivabio.com/. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Statements in this press release that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding: expectations of Artiva Biotherapeutics, Inc. (the “Company”) regarding the potential benefits, accessibility, effectiveness and safety of AlloNK®; the Company’s expectations regarding timing and availability of data from the Phase 1/1b trial or the IIT; and the Company’s future results of operations and financial position, including cash runway. Words such as “believe,” “anticipate,” “plan,” “expect,” “intend,” “will,” “may,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the management of the Company as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks and uncertainties, including business, regulatory, economic and competitive risks and uncertainties about the Company, including, without limitation, risks inherent in developing product candidates, future results from the Company’s ongoing and planned clinical trials, risks related to conducting clinical trials, including delays in activation of clinical trial sites or in subject enrollment, the Company’s ability to obtain adequate financing to fund its planned clinical trials and other expenses, risks that future clinical trial results may not be consistent with interim, initial or preliminary results or results from prior preclinical studies or clinical trials, trends in the industry, the Company’s relationships with its existing and future collaboration partners, the legal and regulatory framework for the industry and future expenditures. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. Other factors that may cause the Company’s actual results to differ from current expectations are discussed in the Company’s filings with the Securities and Exchange Commission (the “SEC”), including the section titled “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this press release is given. Except as required by law, the Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. Artiva Biotherapeutics, Inc.Condensed Balance Sheets(unaudited)(in thousands) June 30, 2024 December 31,2023Assets Cash, cash equivalents and short-term investments$46,556 $76,971 Property and equipment, net 7,315 8,096 Operating and financing lease right-of-use assets 15,420 16,547 Other assets 6,621 3,500 Total assets$75,912 $105,114 Liabilities, convertible preferred stock, and stockholders' deficit Accounts payable and accrued expenses$7,037 $8,631 Operating and financing lease liabilities 15,765 16,912 Simple agreements for future equity (SAFEs) 27,720 25,100 Other liabilities 74 73 Total liabilities 50,596 50,716 Convertible preferred stock 216,413 216,413 Stockholders' deficit (191,097) (162,015)Total liabilities, convertible preferred stock, and stockholders' deficit$75,912 $105,114 Artiva Biotherapeutics, Inc.Condensed Statements of Operation and Comprehensive Loss(unaudited)(in thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenue Collaboration revenue$— $3,497 $— $4,487 License and development support revenue — — 251 — Total revenue — 3,497 251 4,487 Operating expenses: Research and development 12,333 11,262 23,488 26,033 General and administrative 3,857 4,059 7,444 7,965 Total operating expenses 16,190 15,321 30,932 33,998 Loss from operations (16,190) (11,824) (30,681) (29,511)Other income (expense) Interest income 676 509 1,326 1,533 Change in fair value of SAFEs (2,352) — (2,620) — Other income (expense), net 23 31 169 (23)Total other income (expense) (1,653) 540 (1,125) 1,510 Net loss$(17,843) $(11,284) $(31,806) $(28,001)Net loss per share, basic and diluted$(22.00) $(14.09) $(39.24) $(35.12)Weighted-average common shares outstanding, basic and diluted 811,210 800,889 810,484 797,403 Comprehensive loss: Net Loss$(17,843) $(11,284) $(31,806) $(28,001)Other comprehensive income (loss) (86) 127 (187) 127 Comprehensive loss$(17,929) $(11,157) $(31,993) $(27,874) ContactsInvestors: Neha Krishnamohan, Artiva Biotherapeutics, ir@artivabio.comMedia: Jessica Yingling, Ph.D., Little Dog Communications Inc., jessica@litldog.com, +1.858.344.8091

HYDERABAD, India--( BUSINESS WIRE )--Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY; along with its subsidiaries together referred to as “Dr. Reddy’s”), today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the launch of its proposed biosimilar Rituximab candidate DRL_RI (ITUXREDI ® ) in European markets. Dr. Reddy’s had previously received the EU GMP certificate for its Rituximab drug substance and drug product manufacturing facility located in Hyderabad, India. As part of the established approval process, the CHMP positive opinion will now be reviewed by the European Commission (EC), following which a decision will be made on the grant of marketing authorisation in the European Union (EU) member countries, and the European Economic Area (EEA) member states of Norway, Iceland, and Liechtenstein. A Marketing Authorisation Application (MAA) for submission to the UK Medicines and Healthcare products Regulatory Agency (MHRA) will be made separately in keeping with the reliance route under the International Recognition Procedure (IRP). DRL_RI is being developed as a biosimilar of MabThera ® (Rituximab), a cluster of differentiation 20 (CD20) directed cytolytic antibody. ITUXREDI ® / DRL_RI (rituximab) is a proposed biosimilar to reference medicinal product MabThera ® and the intended indications are the same as those currently approved for MabThera®: Non–Hodgkin’s Lymphoma (NHL); Chronic Lymphocytic Leukaemia (CLL); Rheumatoid Arthritis (RA); Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA); Pemphigus Vulgaris (PV). EMA reference product, MabThera®, is a registered trademark of Roche. About Dr. Reddy’s biosimilars programme: Dr. Reddy’s biosimilars business is part of our key strategic initiatives expected to drive both near-term and long-term growth. Over the last 25 years, our Biologics team has developed into a fully integrated organisation with robust capabilities in the development, manufacture and commercialisation of a range of biosimilar products in oncology and immunology. We have a portfolio of commercial products in India, with some products marketed in more than 25 other countries. In addition, we have several products in the pipeline in oncology and auto-immune diseases in various stages of development for global launches across regulated as well as emerging markets. We are also ramping up manufacturing capacity to support our global expansion plans. In July 2023, our proposed rituximab biosimilar application was accepted for review by the USFDA, EMA and MHRA. Earlier this year, we launched Versavo® (bevacizumab) in the UK, making it our first biosimilar product to be approved and launched in that country. About Dr. Reddy’s : Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY) is a global pharmaceutical company headquartered in Hyderabad, India. Established in 1984, we are committed to providing access to affordable and innovative medicines. Driven by our purpose of ‘Good Health Can’t Wait’, we offer a portfolio of products and services including APIs, generics, branded generics, biosimilars and OTC. Our major therapeutic areas of focus are gastrointestinal, cardiovascular, diabetology, oncology, pain management and dermatology. Our major markets include – USA, India, Russia & CIS countries, China, Brazil and Europe. As a company with a history of deep science that has led to several industry firsts, we continue to plan ahead and invest in businesses of the future. As an early adopter of sustainability and ESG actions, we released our first Sustainability Report in 2004. Our current ESG goals aim to set the bar high in environmental stewardship; access and affordability for patients; diversity; and governance. For more information, log on to: www.drreddys.com . Disclaimer: This press release may include statements of future expectations and other forward-looking statements that are based on the management’s current views and assumptions and involve known or unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. In addition to statements which are forward-looking by reason of context, the words "may", "will", "should", "expects", "plans", "intends", "anticipates", "believes", "estimates", "predicts", "potential", or "continue" and similar expressions identify forward-looking statements. Actual results, performance or events may differ materially from those in such statements due to without limitation, (i) general economic conditions such as performance of financial markets, credit defaults , currency exchange rates, interest rates, persistency levels and frequency / severity of insured loss events, (ii) mortality and morbidity levels and trends, (iii) changing levels of competition and general competitive factors, (iv) changes in laws and regulations and in the policies of central banks and/or governments, (v) the impact of acquisitions or reorganization, including related integration issues, and (vi) the susceptibility of our industry and the markets addressed by our, and our customers’, products and services to economic downturns as a result of natural disasters, epidemics, pandemics or other widespread illness, including coronavirus (or COVID-19), and (vii) other risks and uncertainties identified in our public filings with the Securities and Exchange Commission, including those listed under the "Risk Factors" and "Forward-Looking Statements" sections of our Annual Report on Form 20-F for the year ended March 31, 2024. The company assumes no obligation to update any information contained herein.

Data Highlight Positive Outcomes in Uncontrolled Gout With KRYSTEXXA ® and Progress in Addressing Sjögren's Disease THOUSAND OAKS, Calif., June 12, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of data across its diverse portfolio and pipeline at the European Alliance of Associations for Rheumatology's (EULAR) 2024 Congress, June 12-15 in Vienna. The 27 abstracts from Amgen-sponsored and partner-led studies demonstrate Amgen's commitment to improving the lives of patients living with inflammatory and rheumatic disease through the development of novel medicines. Key presentations include the first findings showing dazodalibep improved major biomarkers in Sjögren's disease, as well as data on treatment outcomes for uncontrolled gout based on a post-hoc analysis of the MIRROR trial for KRYSTEXXA® (pegloticase) with methotrexate. "We are deeply committed to advancing patient care through continuous innovation and rigorous science. The data presented at EULAR 2024 further demonstrate our efforts to address complex diseases," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "By advancing scientific research, we are not only enhancing our understanding of these conditions, but also paving the way for more effective treatments that have the potential to significantly improve patient outcomes." Additional presentations include new long-term data from the FOREMOST study of Otezla® (apremilast) in early oligoarticular psoriatic arthritis, as well as a post-hoc analysis of TAVNEOS® (avacopan) versus prednisone taper in patients with severe active MPA/GPA and active ear, nose or throat manifestations. For more information on the Amgen abstracts, see below. Abstracts and Presentation Times: Amgen-Sponsored Abstracts Dazodalibep CD40L blockade with dazodalibep significantly improves disease activity, swollen and tender joint counts, while reducing multiple T- and B-cell biomarkers in the MIDORA phase 2 study of patients with moderate-to-severe active rheumatoid arthritis Abstract #AB0746, Rheumatoid Arthritis (Publication only) Dazodalibep (anti-CD40L) effectively reduces multiple proteins associated with B-, T, and dendritic cell biomarkers in Sjögren's disease: Corroboration of immunophenotyping findings from the ALISS phase 2 study Abstract #OP0058, Clinical Abstract Sessions: New Targets and New Treatments in Sjön's Disease (Oral Abstract Presentations), Wednesday, June 12 from 5:00 to 5:10 p.m. CDT Sjögren's Disease Global burden of Sj ö gren's disease (SjD): Findings from a systematic literature review (SLR) of humanistic and clinical outcomes Abstract #AB0815, Sjögren`s syndrome (Publication Only) KRYSTEXXA® (pegloticase) Achievement of "gout remission" during intensive urate-lowering over 52 weeks of pegloticase therapy Abstract #POS0239, Clinical Poster Tours: Gout treatment in 2024 (Poster Tours), Friday, June 14 at 9:30 a.m. CDT Influence of acute gout flare and serum urate lowering on biomarkers of systemic inflammation Abstract #AB0114, Crystal related disorders (Publication Only) Patient-reported quality of life in uncontrolled gout and changes with intensive urate-lowering: Comparison of tophaceous and non-tophaceous patients Abstract #AB0112, Crystal related disorders (Publication Only) Pre-infusion glucocorticoid reduction/elimination in patients with uncontrolled gout treated with pegloticase and methotrexate: Experience of one community rheumatology practice Abstract #POS0936, Crystal related disorders (Poster View), Friday, June 14 at 9:30 a.m. CDT Uncontrolled Gout Cardiovascular disease, chronic kidney disease, pain, and psychological issues in patients with controlled vs. uncontrolled gout: A retrospective claims-based cohort analysis Abstract #POS0569, Crystal related disorders (Poster View), Wednesday, June 12 at 3:30 p.m. CDT The concept of gout remission as viewed by rheumatologists, nephrologists, and primary care physicians Abstract #POS0269, Clinical Poster Tours: Gout treatment in 2024 (Poster Tours), Friday, June 14 at 9:30 a.m. CDT Treatment patterns and quality of life in patients with controlled and uncontrolled gout Abstract #POS0940, Crystal related disorders (Poster View), Friday, June 14 at 9:30 a.m. CDT Otezla® (apremilast) Apremilast reduces axial inflammation in patients with psoriatic arthritis as assessed by CANDEN MRI scoring: Results from the phase 4 MOSAIC study Abstract #POS0982, Psoriatic arthritis (Poster View), Friday, June 14 at 9:30 a.m. CDT Apremilast reduces inflammation as measured by MRI, clinical outcomes, and patient-reported outcomes in patients with psoriatic arthritis: Results from the phase 4 MOSAIC study Abstract #POS0968, Psoriatic arthritis (Poster View), Friday, June 14 at 9:30 a.m. CDT Apremilast treatment in early oligoarticular psoriatic arthritis (PsA) improves clinical and patient-reported outcomes for up to 48 weeks – Data from the FOREMOST study Abstract #POS0976, Psoriatic arthritis (Poster View), Friday, June 14 at 9:30 a.m. CDT Apremilast for psoriatic arthritis in the Netherlands: Real-world data from the REWARD study Abstract #AB0453, Psoriatic arthritis (Publication Only) The use of disease activity thresholds for the Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire to assess patient perceptions of disease burden in patients with early oligoarticular psoriatic arthritis treated with apremilast in the FOREMOST study Abstract #AB0473, Psoriatic arthritis (Publication Only) Prolia® (denosumab) Comparative effectiveness of denosumab versus bisphosphonates among treatment-experienced postmenopausal women with osteoporosis in the U.S. Medicare program Abstract #POS0089, Clinical Poster Tours: Treatment Options in Metabolic bone diseases and Osteoporosis (Poster Tours), Thursday, June 13 at 9:54 a.m. CDT Comparative effectiveness of denosumab versus zoledronic acid among postmenopausal women with osteoporosis in the U.S. Medicare program Abstract #POS0583, Other diseases (Poster View), Thursday, June 13 at 9:30 a.m. CDT Risk of fragility fracture after long-term discontinuation of osteoporosis treatment in po st-menopausal osteoporosis women in France: A population-based study conducted on the nationwide claim database (SNDS) Abstract #OP0035, Clinical Abstract Sessions: Risk factors and treatment in osteoporosis (Oral Abstract Presentations), Wednesday, June 12 at 4:50 p.m. CDT TAVNEOS® (avacopan) Avacopan versus prednisone taper in patients with ANCA-associated vasculitis and ear, nose, or throat involvement Abstract #OP0174, Clinical Abstract Sessions: Vasculitis across different vessel sizes (Oral Abstract Presentations), Thursday, June 13 at 11:20 a.m. CDT Data from the ADVOCATE trial on 28 patients with ANCA-associated vasculitis who received avacopan without concomitant glucocorticoid use in the first 29 days Abstract #POS0246, Clinical Poster Tours: Miscellaneous in Vasculitis (Poster Tours), Friday, June 14 at 9:36 a.m. CDT UPLIZNA ® ( inebilizumab-cdon ) Burden of glucocorticoid use and associated toxicities in commercially insured adults with IgG4-related disease Abstract #POS0357, Clinical Poster Tours: IgG4 Related Disease (Poster Tours), Friday, June 14 at 2:45 p.m. CDT Insights into the design and study population of MITIGATE: The first multinational randomized controlled clinical trial in IgG4-related disease (IgG4-RD), evaluating the efficacy and safety of inebilizumab Abstract #POS0347, Clinical Poster Tours: IgG4 Related Disease (Poster Tours), Friday, June 14 at 2:45 p.m. CDT Partner-Led Abstracts Sjögren's Disease The use of natural language processing to characterize disease burden: Sexual distress in Sjögren's disease Abstract #AB0793, Sjön`s syndrome (Publication Only) Using social media listening to characterize the flare lexicon in patients with Sjögren's disease Abstract #AB0794, Sjön`s syndrome (Publication Only) TAVNEOS® (avacopan) Safety and effectiveness of avacopan beyond 52 weeks: Experience to date in the Early Access Program (EAP) Abstract #POS0865, Vasculitis, small and medium size vessels (Poster View), Thursday, June 13 at 2:45 p.m. CDT Design of AVACOSTAR: A real-world study of avacopan in ANCA-associated vasculitis (AAV) Abstract #AB1241, Vasculitis, small and medium size vessels (Publication Only) Uncontrolled Gout Osteoporosis in patients with gout in the United States Abstract #POS0563, Crystal related disorders (Poster View), Wednesday, June 12 at 3:30 p.m. CDT About KRYSTEXXA® (pegloticase) KRYSTEXXA ® (pegloticase) is the first and only biologic approved by the FDA to treat adults living with uncontrolled gout, a painful and debilitating inflammatory condition with which people continue to have abnormally high levels of uric acid and symptoms despite the use of conventional therapies. In 2022, the FDA approved expanding labeling to include co-administration with the immunomodulator methotrexate, based on results from the MIRROR randomized controlled trial, which showed significant improvements in efficacy and safety, including a reduction in infusion reactions. About Uncontrolled Gout Gout is a chronic, progressive inflammatory form of arthritis that is caused by high urate levels in the body. Tiny needle-like crystals can form and build up almost anywhere in the body. Patients with uncontrolled gout continue to have high levels of uric acid and ongoing symptoms of gout despite the use of oral urate-lowering therapies. Uncontrolled gout is a chronic, systemic disease, and if not addressed can have significant clinical consequences. KRYSTEXXA U.S. Indication KRYSTEXXA (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated. Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia. KRYSTEXXA U.S. Important Safety Information WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion and generally manifests within 2 hours of the infusion. Delayed hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be premedicated with antihistamines and corticosteroids and closely monitored for anaphylaxis for an appropriate period after administration of KRYSTEXXA. Serum uric acid levels should be monitored prior to each infusion and treatment discontinued if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. Patients at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency should be screened prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency. CONTRAINDICATIONS In patients with G6PD deficiency. In patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components. WARNINGS AND PRECAUTIONS Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including KRYSTEXXA. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated. Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in the pre-marketing placebo-controlled clinical trials experienced exacerbation. Caution should be exercised in patients who have congestive heart failure and patients should be closely monitored following infusion. ADVERSE REACTIONS The most commonly reported adverse reactions (≥5%) are: KRYSTEXXA co-administration with methotrexate trial: gout flares, arthralgia, COVID-19, nausea and fatigue; KRYSTEXXA alone: gout flares, arthralgia, COVID-19, nausea, fatigue, infusion reactions, pain in extremity, hypertension and vomiting. KRYSTEXXA pre-marketing placebo-controlled trials: gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting. Please see Full Prescribing Information, including Boxed Warning. About Otezla® (apremilast) Otezla® (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which Otezla exerts its therapeutic action in patients is not well defined. Since its initial FDA approval in 2014, Otezla has been prescribed to more than 840,000 patients worldwide. About Psoriatic Arthritis Psoriatic arthritis is a chronic, inflammatory form of arthritis, which can cause swelling, stiffness and pain in and around the joints that worsens over time and can decrease physical function. It is estimated that nearly 38 million people worldwide have psoriatic arthritis. Around a third of people living with psoriasis may go on to develop psoriatic arthritis. If left untreated, psoriatic arthritis can cause disability. Otezla U.S. Indications Otezla (apremilast) is indicated for the treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy. Otezla is indicated for the treatment of adult patients with active psoriatic arthritis. Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet's Disease. Otezla U.S. Important Safety Information Contraindications Otezla is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation Warnings and Precautions Hypersensitivity: Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during postmarketing surveillance. If signs or symptoms of serious hypersensitivity reactions occur, discontinue Otezla and institute appropriate therapy Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on Otezla. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur Plaque Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials in patients with moderate to severe plaque psoriasis, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo. Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla attempted suicide; one patient on placebo committed suicide Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo-treated patients (0/495). Two patients who received placebo committed suicide compared to none on Otezla Behçet's Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla Plaque Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients with moderate to severe plaque psoriasis treated with Otezla and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo Behçet's Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and in 3.9% (4/102) of patients taking placebo Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended Adverse Reactions Plaque Psoriasis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache. Overall, the safety profile of Otezla in patients with mild to moderate plaque psoriasis was consistent with the safety profile previously established in adult patients with moderate to severe plaque psoriasis Psoriatic Arthritis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache Behçet's Disease: The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection. Use in Specific Populations Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Please click here for Otezla® Full Prescribing Information. About TAVNEOS® (avacopan) TAVNEOS® (avacopan), approved by the FDA as an adjunctive treatment of severe active ANCA-associated vasculitis (GPA/MPA), is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action. TAVNEOS blocks the complement 5a receptor (C5aR) from binding C5a, the pro-inflammatory complement system fragment. This is presumed to block C5a-mediated neutrophil activation and migration. The precise mechanism of TAVNEOS in ANCA-associated vasculitis (GPA/MPA) has not been definitively established. About ANCA-Associated Vasculitis ANCA-associated vasculitis is an umbrella term for a group of multi-system autoimmune diseases with small vessel inflammation. Inflamed vessels may rupture or become occluded giving rise to a broad array of clinical symptoms and signs related to a systemic inflammatory response which may result in profound impairment in the kidneys, lungs and other organs. Prior to the approval of TAVNEOS in severe active ANCA-associated vasculitis (GPA/MPA), the combination of immunosuppressants most often used for the treatment of ANCA-associated vasculitis (GPA/MPA) include cyclophosphamide or rituximab, combined with daily glucocorticoids (steroids) for prolonged periods, which can be associated with significant clinical consequences. TAVNEOS U.S. Indication TAVNEOS is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use. TAVNEOS U.S. Important Safety Information Contraindications Serious hypersensitivity to avacopan or to any of the excipients. Warning and Precautions Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for six months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions, and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). TAVNEOS is not recommended for patients with active, untreated and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risk and benefit before administering this drug to a patient with liver disease. Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered unless another cause has been established. Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for six months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming. Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection or who have been to places where certain infections are common. Adverse Reactions The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia. Drug Interactions Avoid coadministration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates. Please see Full Prescribing Information and Medication Guide. 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. Amgen 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 Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, 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. 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, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. 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. 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. 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. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Madison Howard, 773-636-4910 (media) Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) SOURCE Amgen