Defibrotide Sodium

– Record total revenues of $4.1 billion in 2024 and $1.1 billion in 4Q24 –– Xywav® and Epidiolex® revenues grew 16% and 15% year-over-year, respectively, in 2024 –– Oncology revenues grew 9% year-over-year in 2024, surpassed $1.1 billion –– Ziihera® approved in 2L HER2+ (IHC3+) BTC; first sales achieved in December 2024 –– 2025 guidance reflects continued top- and bottom-line growth – DUBLIN , Feb. 25, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced financial results for the full year and fourth quarter of 2024 and provided guidance for 2025. "2024 was another strong year as our proven team delivered significant top- and bottom-line growth along with record total revenues of over $4 billion . Our diversified portfolio spanning sleep1, epilepsy and oncology, with each annualizing at over $1 billion , continued to drive growth," said Bruce Cozadd , chairman and chief executive officer, Jazz Pharmaceuticals . "We are pleased with the continued progress of our late-stage pipeline assets, including the recent launch of Ziihera in 2L HER2+ (IHC3+) BTC, upcoming top-line data readout from the HERIZON-GEA-01 trial in 1L GEA, which we now expect in the second half of 2025, and highly encouraging results from the Phase 3 IMforte trial, which we expect to submit as part of an sNDA for Zepzelca® in 1L ES-SCLC in the first half of 2025." Mr. Cozadd continued, "The strength of our 2024 results reinforces our confidence that Jazz is well-positioned to deliver top- and bottom-line growth in 2025 and drive long-term shareholder value. Our focus remains on disciplined capital allocation, which we expect to drive growth of our diversified commercial portfolio, continue advancement of our pipeline and provide flexibility to remain active in corporate development." Key Highlights Total revenues in 2024 grew 6% year-over-year; generated over $1.4 billion in cash from operations. Zanidatamab: Received U.S. FDA approval of and launched Ziihera in 2L HER2+ (IHC3+) BTC. Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 2H25. On track to submit an sNDA in 1H25 for Zepzelca in combination with Tecentriq® (atezolizumab) as maintenance therapy in 1L ES-SCLC based on the potentially practice-changing results from the Phase 3 IMforte trial. Top- and bottom-line growth expected in 2025; 2025 total revenue guidance of $4.15 - $4.40 billion , representing 5% growth at the midpoint. Total revenue guidance is underpinned by expected continued growth in diversified commercial portfolio spanning sleep1, epilepsy and oncology. Received U.S. FDA approval of and launched Ziihera in 2L HER2+ (IHC3+) BTC. Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 2H25. Total revenue guidance is underpinned by expected continued growth in diversified commercial portfolio spanning sleep1, epilepsy and oncology. ________________________________ 1 Total sleep revenue includes: Xywav, branded Xyrem and high-sodium oxybate authorized generic royalty revenues. Business Updates Commercial Updates Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution: Xywav net product sales increased 16% to $1,473.2 million in 2024 and increased 19% to $401.0 million in 4Q24 compared to the same periods in 2023. Meaningful Xywav net patient adds in 4Q24 (approximately 525 patients) with approximately 14,150 active Xywav patients exiting 4Q24, comprised of: Approximately 10,250 narcolepsy patients. Approximately 3,900 idiopathic hypersomnia (IH) patients, with 350 net patient adds. Xywav is the only low-sodium oxybate, the #1 branded treatment for narcolepsy2 and the only FDA-approved therapy to treat IH. Approximately 10,250 narcolepsy patients. Approximately 3,900 idiopathic hypersomnia (IH) patients, with 350 net patient adds. Xyrem® (sodium oxybate) oral solution and high-sodium oxybate authorized generic (AG) royalties: Xyrem net product sales decreased 59% to $233.8 million in 2024 and decreased 54% to $49 .3 million in 4Q24 compared to the same periods in 2023. Royalties from high-sodium oxybate AGs increased by $141 .7 million to $217 .6 million in 2024 and increased $15 .9 million to $55 .3 million in 4Q24, compared to the same periods in 2023. Epidiolex/Epidyolex® (cannabidiol): Epidiolex/Epidyolex net product sales increased 15% to $972.4 million in 2024 and increased 14% to $275.0 million in 4Q24 compared to the same periods in 2023. Outside of the U.S. , Epidyolex is approved in more than 35 countries. Presented data at the American Epilepsy Society 2024 Annual meeting, including novel findings from the BECOME-LTC, BECOME-TSC and EpiCom studies, demonstrating the meaningful impact of Epidiolex in the treatment of patients with rare epilepsies including benefits of Epidiolex's benefits beyond seizure control. Remain confident in achieving blockbuster status for Epidiolex/Epidyolex in 2025. Rylaze®/Enrylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales increased 4% to $410.8 million in 2024 and were in line in 4Q24 compared to the same periods in 2023 despite headwinds from Children's Oncology Group (COG) protocol changes that impacted timing of asparaginase administration. The temporary impact to Rylaze net product sales due to previously announced COG pediatric acute lymphoblastic leukemia (ALL) protocol updates is still expected to normalize by early 2025. Zepzelca (lurbinectedin): Zepzelca net product sales increased 11% to $320.3 million in 2024 and increased 6% to $78.3 million in 4Q24 compared to the same periods in 2023. Based on potentially practice-changing positive results from the Phase 3 IMforte trial, the Company plans to submit a supplemental New Drug Application (sNDA) for Zepzelca's use in combination with Tecentriq as maintenance therapy in first-line (1L) extensive-stage (ES) small cell lung cancer (SCLC) in 1H25. Ziihera (zanidatamab-hrii): Ziihera net product sales were $1.1 million in 2024 and 4Q24 after the initial product launch and availability in December of 2024 following FDA approval in November. Initial positive reception by prescribers with the first patient treated in December. Ziihera added to National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology. Ziihera added to European Society for Medical Oncology ® (ESMO®) Clinical Practice Guidelines for Biliary Tract Cancers. __________________________ 2 Based on 4Q24 Xywav net product sales. Key Pipeline Highlights Zanidatamab: In 4Q24, announced U.S. FDA granted accelerated approval of Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC). The pivotal HERIZON-GEA-01 trial, evaluating zanidatamab in 1L gastroesophageal adenocarcinoma (GEA), is expected to read out in 2H25 based on an updated assessment of progression events. Recruitment for the trial remains on track. Data presented at the San Antonio Breast Cancer Symposium 2024 continued to underscore zanidatamab's potential for patients previously treated with trastuzumab deruxtecan (T-DXd) and showcased the advancement of our clinical program in breast cancer. The Phase 3 EmpowHER-BC-303 trial to evaluate zanidatamab plus chemotherapy or trastuzumab plus chemotherapy in patients with HER2-positive breast cancer whose disease has progressed on previous T-DXd treatment continues to enroll patients. First patient enrolled in the Phase 2 pan-tumor trial to evaluate HER2-positive solid tumors. Financial Highlights Three Months Ended December 31 , Year Ended December 31 , (In thousands, except per share amounts) 2024 2023 2024 2023 Total revenues $ 1,088,173 $ 1,011,935 $ 4,068,950 $ 3,834,204 GAAP net income $ 191,115 $ 94,154 $ 560,120 $ 414,832 Non-GAAP adjusted net income $ 405,863 $ 345,286 $ 1,369,729 $ 1,295,824 GAAP earnings per share $ 3.11 $ 1.42 $ 8.65 $ 6.10 Non-GAAP adjusted EPS $ 6.60 $ 5.02 $ 20.90 $ 18.29 GAAP net income for 2024 was $560.1 million , or $8.65 per diluted share, compared to $414.8 million , or $6.10 per diluted share, for 2023. GAAP net income for 4Q24 was $191.1 million , or $3.11 per diluted share, compared to a GAAP net income of $94.2 million , or $1.42 per diluted share, for 4Q23. Non-GAAP adjusted net income for 2024 was $1,369 .7 million, or $20.90 per diluted share, compared to $1,295 .8 million, or $18.29 per diluted share, for 2023. Non-GAAP adjusted net income for 4Q24 was $405 .9 million, or $6.60 per diluted share, compared to $345 .3 million, or $5.02 per diluted share, for 4Q23. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release. Total Revenues Three Months Ended December 31 , Year Ended December 31 , (In thousands) 2024 2023 2024 2023 Xywav $ 400,964 $ 337,019 $ 1,473,202 $ 1,272,977 Xyrem 49,290 106,721 233,816 569,730 Epidiolex/Epidyolex 275,047 240,622 972,423 845,468 Sativex 5,173 5,137 18,877 19,668 Total Neuroscience 730,474 689,499 2,698,318 2,707,843 Rylaze/Enrylaze 101,487 101,747 410,846 394,226 Zepzelca 78,328 74,010 320,318 289,533 Defitelio/defibrotide 57,650 51,083 216,565 184,000 Vyxeos 53,247 46,912 162,595 147,495 Ziihera 1,051 — 1,051 — Total Oncology 291,763 273,752 1,111,375 1,015,254 Other 2,974 4,088 11,471 13,846 Product sales, net 1,025,211 967,339 3,821,164 3,736,943 High-sodium oxybate AG royalty revenue 55,307 39,387 217,575 75,918 Other royalty and contract revenues 7,655 5,209 30,211 21,343 Total revenues $ 1,088,173 $ 1,011,935 $ 4,068,950 $ 3,834,204 Total revenues increased 6% in 2024 and 8% in 4Q24 compared to the same periods in 2023. Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, was $2,915 .9 million in 2024, an increase of 5% compared to $2,783.8 million in 2023 and $785 .8 million in 4Q24, an increase of 8% compared to $728.9 million in 4Q23. The increase in 2024 and 4Q24 was due to higher Xywav and Epidiolex/Epidyolex net product sales together with increased high-sodium oxybate AG royalty revenue, partially offset by decreased Xyrem net product sales. Oncology net product sales were $1,111 .4 million in 2024, an increase of 9% compared to $1,015 .3 million in 2023 and $291 .8 million in 4Q24, an increase of 7% compared to $273 .8 million in 2023, and included higher net product sales from Defitelio/defibrotide which increased 18% in 2024 and 13% in 4Q24 and Zepzelca which increased 11% in 2024 and 6% in 4Q24. In 4Q24, Rylaze net product sales were negatively impacted due to an update to the COG pediatric treatment protocols for ALL, which impacts the timing of asparaginase administration. Operating Expenses and Effective Tax Rate Three Months Ended December 31 , Year Ended December 31 , (In thousands, except percentages) 2024 2023 2024 2023 GAAP: Cost of product sales $ 128,713 $ 107,243 $ 445,713 $ 435,577 Gross margin 87.4 % 88.9 % 88.3 % 88.3 % Selling, general and administrative $ 369,287 $ 396,034 $ 1,385,294 $ 1,343,105 % of total revenues 33.9 % 39.1 % 34.0 % 35.0 % Research and development $ 240,500 $ 216,608 $ 884,000 $ 849,658 % of total revenues 22.1 % 21.4 % 21.7 % 22.2 % Acquired in-process research and development $ — $ 18,000 $ 10,000 $ 19,000 Income tax benefit1 $ (57,912) $ (33,089) $ (91,429) $ (119,912) Effective tax rate 1 (43.5) % (53.8) % (19.4) % (40.2) % _________________________ 1. The GAAP income tax benefit increased in the three months ended December 31, 2024 , compared to the same period in 2023, primarily due to patent box benefits recognized in the period and decreased in the year ended December 31, 2024 , compared to the same period in 2023, primarily due to the change in income mix across our jurisdictions, partially offset by patent box benefits. Three Months Ended December 31 , Year Ended December 31 , (In thousands, except percentages) 2024 2023 2024 2023 Non-GAAP adjusted: Cost of product sales $ 86,492 $ 71,238 $ 295,897 $ 269,079 Gross margin 91.6 % 92.6 % 92.3 % 92.8 % Selling, general and administrative $ 323,167 $ 300,520 $ 1,226,724 $ 1,110,948 % of total revenues 29.7 % 29.7 % 30.1 % 29.0 % Research and development $ 220,857 $ 201,107 $ 809,327 $ 784,811 % of total revenues 20.3 % 19.9 % 19.9 % 20.5 % Acquired in-process research and development $ — $ 18,000 $ 10,000 $ 19,000 Income tax expense1 $ 308 $ 20,475 $ 131,307 $ 93,260 Effective tax rate1 0.1 % 5.6 % 8.7 % 6.7 % _________________________ 1. The non-GAAP income tax expense decreased in the three months ended December 31, 2024 , compared to the same period in 2023, primarily due to patent box benefits recognized in the period and increased in the year ended December 31, 2024 , compared to the same period in 2023, due to the change in income mix across our jurisdictions, partially offset by patent box benefits. Changes in operating expenses in 2024 and 4Q24 over the prior year periods are primarily due to the following: Cost of product sales, on a GAAP and non-GAAP adjusted basis, increased in 2024 and 4Q24, compared to the same periods in 2023, primarily due to higher inventory provisions and changes in product mix. Cost of product sales, on a GAAP basis, included lower acquisition accounting inventory fair value step up expense in 2024 as compared to the previous period. Selling, general and administrative (SG&A) expenses, on a GAAP and non-GAAP adjusted basis, increased in 2024 compared to the same period in 2023, primarily due to higher compensation-related expenses, increased investment in sales and marketing and increased litigation costs, partially offset, on a GAAP basis, by costs related to impairment of facility assets and program terminations in 2023. SG&A expenses, on a GAAP basis, decreased in 4Q24 compared to the same period in 2023, primarily due to the impairment of facility assets in 4Q23, partially offset by higher compensation related expenses. SG&A expenses, on a non-GAAP adjusted basis, increased in 4Q24 primarily due to higher compensation-related expenses. Research and development (R&D) expenses, on a GAAP and non-GAAP adjusted basis, increased in 2024 and 4Q24, compared to the same period in 2023, primarily due to increased compensation related expenses and clinical study costs primarily related to zanidatamab, partially offset by reduced costs related to JZP150 and JZP385. Acquired in-process research and development (IPR&D) expense in 2024, on a GAAP and non-GAAP adjusted basis, related to an upfront payment made in connection with our asset purchase and collaboration agreement with Redx Pharma plc . Acquired IPR&D expense in 2023, on a GAAP and non-GAAP adjusted basis, primarily related to an upfront payment made in connection with our licensing and collaboration agreement with Autifony Therapeutics Limited . Cash Flow and Balance Sheet As of December 31, 2024 , cash, cash equivalents and investments were $3.0 billion , and the outstanding principal balance of the Company's long-term debt was $6.2 billion . In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $885.0 million . For the year ended December 31, 2024 , the Company generated $1.4 billion of cash from operations reflecting strong business performance and continued financial discipline. In January 2025 , the Company made a voluntary prepayment of $750.0 million principal amount on the Term Loan B. 2025 Financial Guidance Jazz Pharmaceutical's full year 2025 financial guidance is as follows: (In millions) Guidance Total Revenues $4,150 - $4,400 (In millions, except per share amounts and percentages) GAAP Non-GAAP Gross margin % 88 % 92%1,6 SG&A expenses $1,404 - $1,483 $1,250 - $1,310 2,6 R&D expenses $792 - $851 $720 - $770 3,6 Effective tax rate (5)% - 10% 13% - 15%4,6 Net income $560 - $720 $1,400 - $1,500 5,6 Net income per diluted share $9.15 - $11.50 $22.50 - $24.00 5,6 Weighted-average ordinary shares used in per share calculations 62 - 63 62 - 63 ___________________________ 1. Excludes $135-$155 million of amortization of acquisition-related inventory fair value step-up and $14-$16 million of share-based compensation expense. 2. Excludes $154-$173 million of share-based compensation expense. 3. Excludes $72-$81 million of share-based compensation expense. 4. Excludes 18%-5% from the GAAP effective tax rate of (5)%-10% relating to the income tax effect of adjustments between GAAP net income and non-GAAP adjusted net income, resulting in a non-GAAP adjusted effective tax rate of 13%-15%. 5. Beginning with the 2025 financial guidance presented in this press release, the company will no longer include an adjustment for non-cash interest expense in its non-GAAP adjusted financial measures. Accordingly, any historical non-GAAP adjusted financial measures presented by the company in the future, beginning with the company's earnings press release for the first quarter of 2025, will not include an adjustment for non-cash interest expense. Any comparative historical periods presented will also be updated to reflect this change beginning with the company's earnings press release for the first quarter of 2025. However, for purposes of comparability with the company's prior presentations of non-GAAP financial measures, the historical non-GAAP financial measures presented in this press release include an adjustment for non-cash interest expense. 6. See "Non-GAAP Financial Measures" below. Reconciliations of non-GAAP adjusted guidance measures are included above and in the table titled "Reconciliation of GAAP to non-GAAP Adjusted 2025 Net Income Guidance" at the end of this press release. Conference Call Details Jazz Pharmaceuticals will host an investor conference call and live audio webcast today at 4:30 p.m. ET ( 9:30 p.m. GMT ) to provide a business and financial update and discuss its 2024 full year and 4Q24 results and 2025 guidance. Audio webcast/conference call: U.S. Dial-In Number: +1 800 715 9871Ireland Dial-In Number: +353 1800 943 926Additional global dial-in numbers are available here.Passcode: 5080203 Interested parties may access the live audio webcast via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information. Non-GAAP Financial Measures To supplement Jazz Pharmaceuticals' financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), the Company uses certain non-GAAP (also referred to as adjusted or non-GAAP adjusted) financial measures in this press release and the accompanying tables. In particular, the Company presents non-GAAP adjusted net income (and the related per share measure) and its line-item components, as well as certain non-GAAP adjusted financial measures derived therefrom, including non-GAAP adjusted gross margin percentage and non-GAAP adjusted effective tax rate. Non-GAAP adjusted net income (and the related per share measure) and its line-item components exclude from GAAP reported net income (and the related per share measure) and its line-item components certain items, as detailed in the reconciliation tables that follow, and in the case of non-GAAP adjusted net income (and the related per share measure), adjust for the income tax effect of the non-GAAP adjustments. In this regard, the components of non-GAAP adjusted net income, including non-GAAP adjusted cost of product sales, SG&A expenses and R&D expenses, are income statement line items prepared on the same basis as, and therefore components of, the overall non-GAAP adjusted net income measure. The Company believes that each of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors and analysts and that each of these non-GAAP financial measures, when considered together with the Company's financial information prepared in accordance with GAAP, can enhance investors' and analysts' ability to meaningfully compare the Company's results from period to period, to its forward-looking guidance, and to identify operating trends in the Company's business. In addition, these non-GAAP financial measures are regularly used by investors and analysts to model and track the Company's financial performance. Jazz Pharmaceuticals' management also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate the Company's business and to make operating decisions, and compensation of executives is based in part on certain of these non-GAAP financial measures. Because these non-GAAP financial measures are important internal measurements for Jazz Pharmaceuticals' management, the Company also believes that these non-GAAP financial measures are useful to investors and analysts since these measures allow for greater transparency with respect to key financial metrics the Company uses in assessing its own operating performance and making operating decisions. These non-GAAP financial measures are not meant to be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with the Company's consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles in the reconciliation tables that follow. In addition, from time to time in the future there may be other items that the Company may exclude for purposes of its non-GAAP financial measures; and the Company has ceased, and may in the future cease, to exclude items that it has historically excluded for purposes of its non-GAAP financial measures. In this regard, the company has determined that, beginning with the 2025 financial guidance presented in this press release, it will no longer include an adjustment for non-cash interest expense in its non-GAAP adjusted financial measures. Accordingly, any historical non-GAAP adjusted financial measures presented by the company in the future, beginning with the company's earnings press release for the first quarter of 2025, will not include an adjustment for non-cash interest expense. Any comparative historical periods presented will also be updated to reflect this change beginning with the company's earnings press release for the first quarter of 2025. However, for purposes of comparability with the company's prior presentations of non-GAAP financial measures, the historical non-GAAP financial measures presented in this press release include an adjustment for non-cash interest expense. Likewise, the Company may determine to modify the nature of its adjustments to arrive at its non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measures as used by Jazz Pharmaceuticals in this press release and the accompanying tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. Caution Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to: the Company's growth prospects and future financial and operating results, including the Company's 2025 financial guidance and the Company's expectations related thereto and anticipated catalysts; expectations that Xywav will remain the #1 branded treatment for narcolepsy and Epidiolex achieving blockbuster status in 2025; the ability to generate growth and long-term shareholder value; the Company's advancement of pipeline programs and the timing of development activities, regulatory activities and submissions related thereto, including plans to submit a sNDA for Zepzelca in 1L ES-SCLC in the first half of 2025; planned or anticipated clinical trial events, including with respect to initiations, enrollment and data read-outs, and the anticipated timing thereof, including: top-line PFS data from a Phase 3 trial of zanidatamab in 1L GEA; and the Company's development, regulatory and commercialization strategy; the Company's expectations with respect to its products and product candidates and the potential of the Company's products and product candidates and the potential regulatory path related thereto, including Zepzelca's potential to change current practice in 1L ES-SCLC; the Company's capital allocation and corporate development strategy; the potential successful future development, manufacturing, regulatory and commercialization activities; the Company's ability to realize the commercial potential of its products; the Company's net product sales and goals for net product sales from new and acquired products; the Company's views and expectations relating to its patent portfolio, including with respect to expected patent protection, as well as expectations with respect to exclusivity; the Company's clinical trials confirming clinical benefit or enabling regulatory submissions; planned or anticipated regulatory submissions and filings, and the anticipated timing thereof; potential regulatory approvals; and other statements that are not historical facts. These forward-looking statements are based on the Company's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward- looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: maintaining or increasing sales of, and revenue from, Xywav, Rylaze and Epidiolex/Epidyolex and other marketed products; the introduction of new products into the U.S. market that compete with, or otherwise disrupt the market for the Company's products and product candidates; effectively launching and commercializing the Company's other products and product candidates; the successful completion of development and regulatory activities with respect to the Company's product candidates, obtaining and maintaining adequate coverage and reimbursement for the Company's products; the time-consuming and uncertain regulatory approval process, including the risk that the Company's current and/or planned regulatory submissions may not be submitted, accepted or approved by applicable regulatory authorities in a timely manner or at all; the costly and time-consuming pharmaceutical product development and the uncertainty of clinical success, including risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients; global economic, financial, and healthcare system disruptions and the current and potential future negative impacts to the Company's business operations and financial results; geopolitical events, including international tariffs and the conflict between Russia and Ukraine and related sanctions; macroeconomic conditions, including global financial markets, rising interest rates and inflation and recent and potential banking disruptions; regulatory initiatives and changes in tax laws; market volatility; protecting and enhancing the Company's intellectual property rights and the Company's commercial success being dependent upon the Company obtaining, maintaining and defending intellectual property protection and exclusivity for its products and product candidates; delays or problems in the supply or manufacture of the Company's products and product candidates; complying with applicable U.S. and non- U.S. regulatory requirements, including those governing the research, development, manufacturing and distribution of controlled substances; government investigations, legal proceedings and other actions; identifying and consummating corporate development transactions, financing these transactions and successfully integrating acquired product candidates, products and businesses; the Company's ability to realize the anticipated benefits of its corporate development transactions and its collaborations and license agreements with third parties; the sufficiency of the Company's cash flows and capital resources; the Company's ability to achieve targeted or expected future financial performance and results and the uncertainty of future tax, accounting and other provisions and estimates; the Company's ability to meet its projected long-term goals and objectives, in the time periods that the Company anticipates, or at all, and the inherent uncertainty and significant judgments and assumptions underlying the Company's long-term goals and objectives; fluctuations in the market price and trading volume of the Company's ordinary shares; the timing and availability of alternative investment opportunities; and other risks and uncertainties affecting the Company, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports, including the Company's Annual Report on Form 10-K for the year ended December 31, 2024 , and future filings and reports by the Company. Other risks and uncertainties of which the Company is not currently aware may also affect the Company's forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. JAZZ PHARMACEUTICALS PLC CONDENSED CONSOLIDATED STATEMENTS OF INCOME(In thousands, except per share amounts)(Unaudited) Three Months Ended December 31 , Year Ended December 31 , 2024 2023 2024 2023 Revenues: Product sales, net $ 1,025,211 $ 967,339 $ 3,821,164 $ 3,736,943 Royalties and contract revenues 62,962 44,596 247,786 97,261 Total revenues 1,088,173 1,011,935 4,068,950 3,834,204 Operating expenses: Cost of product sales (excluding amortization of acquired developed technologies) 128,713 107,243 445,713 435,577 Selling, general and administrative 369,287 396,034 1,385,294 1,343,105 Research and development 240,500 216,608 884,000 849,658 Intangible asset amortization 158,903 151,553 627,313 608,284 Acquired in-process research and development — 18,000 10,000 19,000 Total operating expenses 897,403 889,438 3,352,320 3,255,624 Income from operations 190,770 122,497 716,630 578,580 Interest expense, net (51,256) (70,324) (238,097) (289,438) Foreign exchange gain (loss) (6,295) 9,353 (8,182) 8,787 Income before income tax benefit and equity in loss ofinvestees 133,219 61,526 470,351 297,929 Income tax benefit (57,912) (33,089) (91,429) (119,912) Equity in loss of investees 16 461 1,660 3,009 Net income $ 191,115 $ 94,154 $ 560,120 $ 414,832 Net income per ordinary share: Basic $ 3.16 $ 1.50 $ 9.06 $ 6.55 Diluted $ 3.11 $ 1.42 $ 8.65 $ 6.10 Weighted-average ordinary shares used in per share calculations - basic 60,538 62,578 61,838 63,291 Weighted-average ordinary shares used in per share calculations - diluted 61,503 69,673 66,007 72,066 JAZZ PHARMACEUTICALS PLC CONDENSED CONSOLIDATED BALANCE SHEETS(In thousands)(Unaudited) December 31 ,2024 December 31 ,2023 ASSETS Current assets: Cash and cash equivalents $ 2,412,864 $ 1,506,310 Investments 580,000 120,000 Accounts receivable, net of allowances 716,765 705,794 Inventories 480,445 597,039 Prepaid expenses 177,411 185,476 Other current assets 261,543 320,809 Total current assets 4,629,028 3,435,428 Property, plant and equipment, net 173,413 169,646 Operating lease assets 53,582 65,340 Intangible assets, net 4,755,695 5,418,039 Goodwill 1,716,323 1,753,130 Deferred tax assets, net 560,245 477,834 Deferred financing costs 9,489 6,478 Other non-current assets 114,482 67,464 Total assets $ 12,012,257 $ 11,393,359 LIABILITIES AND SHAREHOLDERS' EQUITY Current liabilities: Accounts payable $ 77,869 $ 102,750 Accrued liabilities 910,947 793,914 Current portion of long-term debt 31,000 604,954 Income taxes payable 18,757 35,074 Total current liabilities 1,038,573 1,536,692 Long-term debt, less current portion 6,077,640 5,107,988 Operating lease liabilities, less current portion 38,938 59,225 Deferred tax liabilities, net 676,736 847,706 Other non-current liabilities 86,614 104,751 Total shareholders' equity 4,093,756 3,736,997 Total liabilities and shareholders' equity $ 12,012,257 $ 11,393,359 JAZZ PHARMACEUTICALS PLC SUMMARY OF CASH FLOWS (In thousands)(Unaudited) Year Ended December 31 , 2024 2023 Net cash provided by operating activities $ 1,395,908 $ 1,092,007 Net cash used in investing activities (508,195) (163,062) Net cash provided by (used in) financing activities 20,516 (305,254) Effect of exchange rates on cash and cash equivalents (1,675) 1,137 Net increase in cash and cash equivalents $ 906,554 $ 624,828 JAZZ PHARMACEUTICALS PLC RECONCILIATIONS OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATION(In thousands, except per share amounts)(Unaudited) Three Months Ended December 31 , Year Ended December 31 , 2024 2023 2024 2023 Net Income DilutedEPS1 Net Income Diluted EPS1 NetIncome DilutedEPS1 NetIncome Diluted EPS1 GAAP reported $ 191,115 $ 3.11 $ 94,154 $ 1.42 $ 560,120 $ 8.65 $ 414,832 $ 6.10 Intangible asset amortization 158,903 2.58 151,553 2.18 627,313 9.50 608,284 8.44 Share-based compensation expense 70,190 1.14 52,941 0.76 248,045 3.76 226,841 3.15 Acquisition accountinginventory fair value step-up 37,794 0.61 32,352 0.46 135,014 2.05 151,446 2.10 Other costs2 — — 61,727 0.89 — — 85,215 1.18 Non-cash interest expense3 6,081 0.10 6,123 0.09 21,973 0.33 22,378 0.31 Income tax effect of above adjustments (58,220) (0.94) (53,564) (0.77) (222,736) (3.37) (213,172) (2.95) Effect of assumed conversion of the 2024 Notes and the2026 Notes1 — — — (0.01) — (0.02) — (0.04) Non-GAAP adjusted $ 405,863 $ 6.60 $ 345,286 $ 5.02 $ 1,369,729 $ 20.90 $ 1,295,824 $ 18.29 Weighted-average ordinaryshares used in diluted per share calculations - GAAP and non-GAAP1 61,503 69,673 66,007 72,066 ________________________________________________ Explanation of Adjustments and Certain Line Items: 1. Diluted EPS was calculated using the "if-converted" method in relation to the 1.50% exchangeable senior notes due 2024, or the 2024 Notes and the 2.000% exchangeable senior notes due 2026, or the 2026 Notes. In August 2023 and July 2024 , we made irrevocable elections to net share settle the 2024 Notes and the 2026 Notes, respectively. As a result, the assumed issuance of ordinary shares upon exchange of the 2024 Notes and the 2026 Notes have only been included in the calculation of diluted net income per ordinary share, on a GAAP and on a non-GAAP adjusted basis, in each period up to the date each irrevocable election was made. Net income per diluted share, on a GAAP and on a non-GAAP adjusted basis, for the year ended December 31, 2024 , included 3.5 million shares related to the assumed conversion of the 2026 Notes and the associated interest expense, net of tax, add-back to GAAP reported net income and non-GAAP adjusted net income of $10.8 million and $9.7 million , respectively. Net income per diluted share, on a GAAP and on a non-GAAP adjusted basis, for the three months and the year ended December 31, 2023 included 6.4 million shares and 8.0 million shares, respectively, related to the assumed conversion of the 2024 Notes and the 2026 Notes and the associated interest expense, net of tax, add-back to GAAP reported net income of $4.9 million and $24.9 million , respectively, and the associated interest expense, net of tax, add-back to non-GAAP adjusted net income of $4.4 million and $22.2 million , respectively. 2. Includes costs related to the impairment of facility assets and program terminations. 3. Non-cash interest expense associated with debt issuance costs. JAZZ PHARMACEUTICALS PLC RECONCILIATIONS OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATIONCERTAIN LINE ITEMS - FOR THE THREE MONTHS ENDED DECEMBER 31, 2024 AND 2023(In thousands, except percentages)(Unaudited) Three months ended December 31, 2024 Cost ofproductsales Grossmargin Selling, general andadministrative Researchanddevelopment Intangible assetamortization Interestexpense, net Income tax expense (benefit) Effectivetax rate GAAP Reported $ 128,713 87.4 % $ 369,287 $ 240,500 $ 158,903 $ 51,256 $ (57,912) (43.5) % Non-GAAP Adjustments: Intangible asset amortization — — — — (158,903) — — — Share-based compensationexpense (4,427) 0.5 (46,120) (19,643) — — — — Acquisition accountinginventory fair value step-up (37,794) 3.7 — — — — — — Non-cash interest expense — — — — — (6,081) — — Income tax effect of above adjustments — — — — — — 58,220 43.6 Total of non-GAAP adjustments (42,221) 4.2 (46,120) (19,643) (158,903) (6,081) 58,220 43.6 Non-GAAP Adjusted $ 86,492 91.6 % $ 323,167 $ 220,857 $ — $ 45,175 $ 308 0.1 % Three months ended December 31, 2023 Cost ofproductsales Gross margin Selling, general and administrative Research anddevelopment Intangibleassetamortization AcquiredIPR&D Interest expense, net Income tax expense(benefit) Effective tax rate GAAP Reported $ 107,243 88.9 % $ 396,034 $ 216,608 $ 151,553 $ 18,000 $ 70,324 $ (33,089) (53.8) % Non-GAAP Adjustments: Intangible asset amortization — — — — (151,553) — — — — Share-based compensationexpense (3,653) 0.4 (33,787) (15,501) — — — — — Restructuring and othercosts — — (61,727) — — — — — — Non-cash interest expense — — — — — — (6,123) — — Acquisition accountinginventory fair value step-up (32,352) 3.3 — — — — — — — Income tax effect of aboveadjustments — — — — — — — 53,564 59.4 Total of non-GAAP adjustments (36,005) 3.7 (95,514) (15,501) (151,553) — (6,123) 53,564 59.4 Non-GAAP Adjusted $ 71,238 92.6 % $ 300,520 $ 201,107 $ — $ 18,000 $ 64,201 $ 20,475 5.6 % JAZZ PHARMACEUTICALS PLC RECONCILIATIONS OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATIONCERTAIN LINE ITEMS - FOR THE YEAR ENDED DECEMBER 31, 2024 AND 2023(In thousands, except percentages)(Unaudited) Year ended December 31, 2024 Cost of product sales Gross margin Selling, general andadministrative Research and development Intangible assetamortization AcquiredIPR&D Interest expense, net Income tax expense(benefit) Effective tax rate GAAP Reported $ 445,713 88.3 % $ 1,385,294 $ 884,000 $ 627,313 $ 10,000 $ 238,097 $ (91,429) (19.4) % Non-GAAP Adjustments: Intangible asset amortization — — — — (627,313) — — — — Share-based compensation expense (14,802) 0.5 (158,570) (74,673) — — — — — Non-cash interest expense — — — — — — (21,973) — — Acquisition accounting inventory fairvalue step-up (135,014) 3.5 — — — — — — — Income tax effect of above adjustments — — — — — — — 222,736 28.1 Total of non-GAAP adjustments (149,816) 4.0 (158,570) (74,673) (627,313) — (21,973) 222,736 28.1 Non-GAAP Adjusted $ 295,897 92.3 % $ 1,226,724 $ 809,327 $ — $ 10,000 $ 216,124 $ 131,307 8.7 % Year ended December 31, 2023 Cost ofproduct sales Gross margin Selling, general and administrative Research and development Intangible asset amortization AcquiredIPR&D Interest expense, net Income tax expense (benefit) Effective tax rate GAAP Reported $ 435,577 88.3 % $ 1,343,105 $ 849,658 $ 608,284 $ 19,000 $ 289,438 $ (119,912) (40.2) % Non-GAAP Adjustments: Intangible asset amortization — — — — (608,284) — — — — Share-based compensation expense (15,052) 0.4 (146,942) (64,847) — — — — — Other costs — — (85,215) — — — — — — Non-cash interest expense — — — — — — (22,378) — — Acquisition accounting inventory fair value step-up (151,446) 4.1 — — — — — — — Income tax effect of above adjustments — — — — — — — 213,172 46.9 Total of non-GAAP adjustments (166,498) 4.5 (232,157) (64,847) (608,284) — (22,378) 213,172 46.9 Non-GAAP Adjusted $ 269,079 92.8 % $ 1,110,948 $ 784,811 $ — $ 19,000 $ 267,060 $ 93,260 6.7 % JAZZ PHARMACEUTICALS PLC RECONCILIATION OF GAAP TO NON-GAAP ADJUSTED 2025 NET INCOME AND DILUTED EPS GUIDANCE(In millions, except per share amounts)(Unaudited) Net Income Diluted EPS GAAP guidance $560 - $720 $9.15 - $11.50 Intangible asset amortization 610 - 660 9.70 - 10.60 Acquisition accounting inventory fair value step-up 135 - 155 2.15 - 2.50 Share-based compensation expense 240 - 270 3.80 - 4.35 Income tax effect of above adjustments (215) - (235) (3.40) - (3.75) Non-GAAP guidance $1,400 - $1,500 $22.50 - $24.00 Weighted-average ordinary shares used in per share calculations - GAAP and non-GAAP 62 - 63 Contacts: Investors: Jeff Macdonald Executive Director, Investor Relations Jazz Pharmaceuticals plc InvestorInfo@jazzpharma.com Ireland +353 1 634 3211 U.S. +1 650 496 2717 Media: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc CorporateAffairsMediaInfo@jazzpharma.com Ireland +353 1 637 2141 U.S. +1 215 867 4948 View original content to download multimedia:https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-full-year-and-fourth-quarter-2024-financial-results-and-provides-2025-financial-guidance-302385001.html SOURCE Jazz Pharmaceuticals plc

– Results Demonstrate Marked Survival Superiority of Narsoplimab-Treated EAP Patients, in Stand-Alone and Combined Analyses with Narsoplimab Pivotal Trial Patients, over External Control Patients – Results of statistical analyses of survival in narsoplimab-treated expanded access program (EAP) TA-TMA patients compared to similarly at-risk external control registry patients were consistent with those of previously reported analyses comparing survival between narsoplimab-treated OMS721-TMA-001 pivotal trial and external control registry patients The analyses conducted on the combined population of the 49 previously untreated high-risk adult (at least 16 years of age) allogeneic-transplant EAP patients and the 28 OMS721-TMA-001 patients were the same as the complete set of primary statistical and sensitivity analyses comparing survival in the narsoplimab pivotal trial to the external control TA-TMA patients, with representative analyses demonstrating that: Narsoplimab reduced the risk of mortality in high-risk TA-TMA patients by over 2-fold (hazard ratio = 0.46 [95 percent confidence interval:0.30, 0.60]) to approximately 3-fold (hazard ratio = 0.34 [95 percent confidence interval: 0.21, 0.53]) P-values ranged from 0.00002 to less than 0.00001 Narsoplimab reduced the risk of mortality in high-risk TA-TMA patients by over 2-fold (hazard ratio = 0.46 [95 percent confidence interval:0.30, 0.60]) to approximately 3-fold (hazard ratio = 0.34 [95 percent confidence interval: 0.21, 0.53]) P-values ranged from 0.00002 to less than 0.00001 In the EAP allogeneic transplant population, 16 adult and 20 pediatric high-risk TA-TMA patients had failed one or more treatment regimens – most commonly eculizumab – prior to receiving narsoplimab, with 1-year survival of 41 and 47 percent, respectively – over 2-fold higher than the less-than-20-percent historical 1-year survival for patients who fail targeted TA-TMA therapy These results complete the set of independently conducted analyses for inclusion in the narsoplimab BLA resubmission to FDA planned for later this quarter and in the MAA submission to European regulators targeted by mid-year. Together with the previously reported primary and sensitivity analyses, the results are uniformly robust and support the clinical benefit of narsoplimab in TA-TMA, a life-threatening complication of hematopoietic stem cell transplantation with no currently approved treatment SEATTLE--(BUSINESS WIRE)--Feb. 20, 2025-- Omeros Corporation (Nasdaq: OMER) today announced statistical analysis results related to the expanded access program (EAP) for narsoplimab, Omeros’ first-in-class monoclonal antibody inhibiting the lectin pathway of complement, in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), a life-threatening complication in both adult and pediatric hematopoietic stem cell transplantation (HSCT). These latest analyses, conducted by an independent statistical group, comprise multiple survival comparisons between narsoplimab-treated EAP patients and similarly at-risk TA-TMA patients in the external control registry. The results from these analyses further support the robustness of the previously reported results from the statistical analysis plan agreed with FDA, with representative analyses of the combined EAP and pivotal trial patients yielding hazard ratios ranging from 0.34 (95 percent confidence interval: 0.21, 0.53) to 0.46 (95 percent confidence interval: 0.35, 0.60) and p-values ranging from less than 0.00001 to 0.00002. Consistent with all previous clinical experience with narsoplimab, no safety signals of concern were observed. “The results from the expanded access program are further compelling evidence of the effectiveness of narsoplimab in TA-TMA,” stated Miguel-Angel Perales, MD, Chief of the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center and immediate past President of the American Society for Transplantation and Cellular Therapy. “The EAP accepted all-comers globally – adult and pediatric patients in the real-world setting. Many are representative of the most challenging patients that we at MSKCC and the community of transplant experts worldwide regularly attempt to treat. With the now overwhelming clinical survival data and the absence of any identified safety signal, there is a clear need for narsoplimab in the treatment of our patients with TA-TMA, and we look forward to the drug’s rapid approval.” As reported on December 19, 2024 and January 15, 2025, narsoplimab met its primary endpoint, with TA-TMA patients in its OMS721-TMA-001 pivotal trial demonstrating clinically meaningful and statistically significant superiority in overall survival – a hazard ratio of 0.32 (95 percent confidence interval: 0.23 to 0.44) with p-value less than 0.00001 – compared to the TA-TMA patients in the external control registry, with the prespecified primary-related sensitivity analyses strongly supporting the robustness of the primary analysis results. Today’s announcement reports the results of this same set of analyses on patients treated with narsoplimab in the EAP. Overall survival in the primary, primary-related, and EAP-related analyses includes an adjustment for immortal time bias. The narsoplimab EAP population at time of database lock included 136 TA-TMA patients, 128 of whom had received allogeneic versus autologous stem cell transplants. Of those allogeneic graft recipients, 84 were adult (at least 16 years of age) and 44 were children. TA-TMA risk factors are not available for all EAP patients; based on available information and using the international expert consensus criteria for high risk of death (Schoettler et al, 2023), 102 patients (65 adults and 37 children) were characterized as having “high-risk” TA-TMA, with 82 percent of adults and 86 percent of children having multiple risk factors for death. Of the 102 high-risk EAP patients, 49 adults and 13 children had received no treatment prior to narsoplimab. The narsoplimab pivotal trial (OMS721-TMA-001) enrolled 28 adult allogeneic transplant patients with high-risk TA-TMA, none of whom received prior treatment for TA-TMA. The external control registry is comprised of 121 adult patients (defined by the registry as 16 years of age or older) who underwent allogeneic transplant and developed high-risk TA-TMA, none of whom received narsoplimab, any other complement inhibitor treatment, or defibrotide. The following are representative analyses, conducted by the independent statistical group, of the 77 (49 EAP and 28 OMS721-TMA-001) allogeneic HSCT, previously untreated, high-risk adult patients who received narsoplimab compared to similarly at-risk external control registry patients; the first is the same as the previously reported primary analysis and the subsequent 4 are the same as the previously reported primary-related sensitivity analyses, all of which were prespecified in the FDA-agreed statistical analysis plan: 1. Overall survival using Inverse Probability of Treatment Weighting (IPTW) with all specified risk factors: Hazard ratio = 0.37 (95 percent confidence interval: 0.28, 0.48) P-value < 0.00001 2. Overall survival using IPTW with only treatment as a factor: Hazard ratio = 0.46 (95 percent confidence interval: 0.35, 0.60) P-value < 0.00001 3. Testing proportional hazards assumptions using IPTW in a sequence of four models in which patient follow-up is truncated at 100 days, 6 months, 1 year, and 2 years: 100 days: Hazard ratio = 0.46 (95 percent confidence interval: 0.33, 0.63) P-value < 0.00001 6 months: Hazard ratio = 0.40 (95 percent confidence interval: 0.29, 0.54) P-value < 0.00001 1 year: Hazard ratio = 0.37 (95 percent confidence interval: 0.28, 0.50) P-value < 0.00001 2 years: Hazard ratio = 0.36 (95 percent confidence interval: 0.27, 0.48) P-value < 0.00001 4. Overall survival using IPTW with day zero for the external control registry patients set at the median time between the date of TA-TMA diagnosis and the date of narsoplimab treatment initiation for the patients in the combined EAP and OMS721-TMA-001 pivotal trial population: Hazard ratio = 0.36 (95 percent confidence interval: 0.28, 0.48) P-value < 0.00001 5. Overall survival with and without all specified risk factors (RFs) using 1:1* propensity score matching (combined EAP and OMS721-TMA-001 trial patients versus external control registry patients): 1:1 with RFs: Hazard ratio = 0.34 (95 percent confidence interval: 0.21, 0.53) P-value < 0.00001 1:1 w/out RFs: Hazard ratio = 0.39 (95 percent confidence interval: 0.26, 0.60) P-value = 0.00002 *In the previously reported primary and primary-related sensitivity analyses, this analysis included 1:2 propensity score matching. The 121 external control patients, however, do not allow for 1:2 matching vs. 77 narsoplimab-treated patients. Sixteen adult and 20 pediatric allogeneic-transplant EAP patients with high-risk TA-TMA had failed treatment with one or more regimens of eculizumab, ravulizumab, pegcetacoplan, and/or defibrotide prior to administration of narsoplimab. Less than 20 percent of patients who fail these treatments are reported to reach 1-year survival. Despite this historically poor expectation, narsoplimab treatment showed the following 1-year survival in previously treated high-risk EAP patients: All: 44 percent Adult: 41 percent Children: 47 percent In the EAP, 49 adult and 13 pediatric allogeneic-transplant patients with high-risk TA-TMA did not receive complement C5 (e.g., eculizumab, ravulizumab), C3 inhibitors (e.g., pegcetacoplan), or defibrotide prior to treatment with narsoplimab. One-year survival in these patients is: All: 62 percent Adult: 58 percent Children: 79 percent “The EAP results of narsoplimab treatment for TA-TMA are exceptional, both for patients who received narsoplimab as first-line treatment and particularly in patients refractory to prior complement inhibition therapies,” stated Michelle Schoettler, MD, Assistant Professor of Pediatric Oncology and Hematopoietic Cellular Therapy at Emory University. “One-year survival in children with high-risk TA-TMA treated with narsoplimab via the EAP as a front-line agent was an impressive 79 percent and 58 percent in adults. Just as striking were results in patients previously refractory to complement inhibition, who historically had 1-year survival rates of less than 20 percent. In contrast, 1-year survival in refractory children and adults in the EAP cohort with high-risk features treated with narsoplimab (n=36) was 44 percent; more than doubling historic cohorts. These promising results suggest that narsoplimab will be an important therapeutic option for pediatric and adult hematopoietic cell transplant recipients. I look forward to publishing and further detailing the benefits of narsoplimab in children and adults enrolled in the EAP.” In addition to the manuscript on EAP-related analyses, an international group of transplant experts is preparing a manuscript directed to the primary endpoint-related analyses for submission to peer-reviewed journals. “We are pleased to see the results of the narsoplimab EAP analyses for our BLA resubmission,” said Gregory A. Demopulos, M.D., Omeros’ Chairman and Chief Executive Officer. “The EAP-related and primary sensitivity analyses uniformly support the positive results of the primary endpoint – narsoplimab demonstrating clinically meaningful and statistically significant superiority in overall survival compared to the external control. The next step is resubmission of our BLA followed by the planned submission of the narsoplimab MAA for European approval. There is more work to be done, but the entire Omeros team is driving hard to achieve approval and to launch narsoplimab, with the goal of making the drug available to patients and their transplant physicians worldwide.” About Narsoplimab Narsoplimab, also known as “OMS721,” is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, inhibition of MASP-2 has been demonstrated to leave intact the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. A biologics license application (BLA) is pending before the FDA for use of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). Omeros will resubmit the BLA for narsoplimab in TA-TMA followed by our planned submission of the corresponding European marketing authorisation application (MAA) in 2025. FDA has granted narsoplimab breakthrough therapy and orphan drug designations for TA-TMA and orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies. The European Medicines Agency (EMA) has granted orphan drug designation to narsoplimab for treatment in hematopoietic stem-cell transplant. About Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a significant and often lethal complication of stem cell transplantation. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by conditioning regimens, immunosuppressant therapies, infection, graft-versus-host disease, and other factors associated with stem cell transplantation. Endothelial damage, which activates the lectin pathway of complement, plays a central role in the development of TA-TMA. The condition occurs in both autologous and allogeneic transplants but is more common in the allogeneic population. In the United States and Europe, approximately 30,000 allogeneic transplants are performed annually. Recent reports in both adult and pediatric allogeneic stem cell transplant populations have found an approximately 40-percent incidence of TA-TMA, and high-risk features may be present in up to 80 percent of these patients. In severe cases of TA-TMA, mortality can exceed 90 percent and, even in those who survive, long-term renal sequalae (e.g., dialysis) are common. There is no approved therapy or standard of care for TA-TMA. About Omeros Corporation Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing first-in-class small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders, including complement-mediated diseases and cancers, as well as addictive and compulsive disorders. Omeros’ lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application pending before FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. Omeros’ long-acting MASP-2 inhibitor OMS1029 has successfully completed Phase 1 single- and multiple-ascending dose clinical studies. Zaltenibart, Omeros’ inhibitor of MASP-3, the key activator of the alternative pathway of complement, is advancing toward Phase 3 clinical trials for paroxysmal nocturnal hemoglobinuria and complement 3 glomerulopathy. Funded by the National Institute on Drug Abuse, Omeros’ lead phosphodiesterase 7 inhibitor OMS527 is in clinical development for the treatment of cocaine use disorder. Omeros also is advancing a broad portfolio of five novel cellular and molecular immuno-oncology programs. For more information about Omeros and its programs, visit www.omeros.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the “safe harbor” created by those sections for such statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “likely,” “look forward to,” “may,” “objective,” “plan,” “potential,” “predict,” “project,” “should,” “slate,” “target,” “will,” “would” and similar expressions and variations thereof. Forward-looking statements, including statements regarding the anticipated resubmission of the BLA for narsoplimab in the United States and the submission of a marketing authorization application with the EMA, the timing and outcomes of regulatory events, the availability and outcomes of additional analyses, the prospects for obtaining FDA or EMA approval of narsoplimab in any indication, expectations regarding future cash expenditures, and expectations regarding the sufficiency and availability of our capital resources to fund current and planned operations, including the potential commercialization of narsoplimab if it is approved by FDA or the EMA, are based on management’s beliefs and assumptions and on information available to management only as of the date of this press release. Omeros’ actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, unfavorable, unexpected or inconclusive results of our statistical analyses relating to an external registry of TA-TMA patients, potential differences between the diagnostic criteria used in our pivotal trial and in the external registry, and whether FDA and the EMA determine the registry used in our statistical analysis is sufficiently representative of TA-TMA patients, unanticipated or unexpected outcomes of regulatory processes in relevant jurisdictions, unproven preclinical and clinical development activities, our financial condition and results of operations, regulatory processes and oversight, challenges associated with manufacture or supply of our products to support clinical trials, regulatory inspections and/or commercial sale following any marketing approval, changes in reimbursement and payment policies by government and commercial payers or the application of such policies, intellectual property claims, competitive developments, litigation, and the risks, uncertainties and other factors described under the heading “Risk Factors” in our Annual Report on Form 10-K filed with the Securities and Exchange Commission on April 1, 2024, an in our subsequently filed Quarterly Reports on Form 10-Q. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. Dr. Miguel-Angel Perales has previously received advisory services compensation from, and holds a financial interest in, Omeros. Dr. Michelle Schoettler has previously received advisory services compensation from Omeros. View source version on businesswire.com: https://www.businesswire.com/news/home/20250220420439/en/ Jennifer Cook Williams Cook Williams Communications, Inc. Investor and Media Relations IR@omeros.com Source: Omeros Corporation