Defibrotide Sodium

– Total revenues of $898 million in 1Q25 –– Xywav® and Epidiolex® revenues grew 9% and 10% year-over-year, respectively, in 1Q25 –– Completed submission of sNDA for Zepzelca® in 1L ES-SCLC –– Affirming 2025 revenue guidance; updating financial guidance to reflect Chimerix acquisition and impact of certain Xyrem® antitrust litigation settlements – DUBLIN , May 6, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced financial results for the first quarter of 2025 and updated financial guidance for 2025. "In the first quarter of 2025, our focus on commercial execution resulted in total revenues of $898 million , led by the strong performance of Xywav and Epidiolex. In addition, our team continues to receive positive feedback from healthcare providers on the launch of Ziihera® in its first approved indication of 2L HER2+ BTC. We are affirming our 2025 total revenue guidance range of $4.15 - $4.40 billion, reflecting our confidence in our commercial portfolio delivering top-line growth this year," said Bruce Cozadd , chairman and chief executive officer, Jazz Pharmaceuticals . "We continue to make meaningful progress across our pipeline. We are pleased to report that we have submitted a supplemental New Drug Application for Zepzelca for maintenance therapy in first-line extensive-stage small cell lung cancer. In addition, we recently completed the acquisition of Chimerix, adding a near-term commercial opportunity to our late-stage pipeline that addresses a significant unmet need for patients with H3 K27M-mutant diffuse glioma, a rare, high-grade brain tumor that most commonly affects children and young adults. We also advanced multiple trials across our zanidatamab development program and expect top-line data readout from the HERIZON-GEA-01 trial in 1L GEA in the second half of 2025." Key Highlights Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 2H25. Submitted sNDA for Zepzelca in combination with atezolizumab (Tecentriq®) as maintenance therapy in 1L ES-SCLC based on the potentially practice-changing results from the Phase 3 IMforte trial. Data from trial to be presented at the 2025 ASCO Annual Meeting in June 2025 . Acquisition of Chimerix added dordaviprone to late-stage pipeline, representing near-term commercial opportunity; PDUFA target data of August 18, 2025 . Top-line growth expected in 2025; affirmed 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 of Jazz's diversified commercial portfolio. Total revenue guidance is underpinned by expected continued growth of Jazz's diversified commercial portfolio. Business Updates Commercial Updates Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution: Xywav net product sales increased 9% to $344.8 million in 1Q25 compared to 1Q24. Meaningful Xywav net patient adds in 1Q25 (approximately 450 patients) with approximately 14,600 active Xywav patients exiting 1Q25, comprised of: Approximately 10,375 narcolepsy patients. Approximately 4,225 idiopathic hypersomnia (IH) patients, with 325 net patient adds. Two presentations at the American Academy of Neurology Annual Meeting provided updated results from the open-label, single-arm, Phase 4 DUET trial of adults with narcolepsy or IH. The results demonstrated statistically significant improvements from baseline to end of treatment in Epworth Sleepiness Scale (ESS) scores, reduced sleep stage shifts, increased deep sleep and reduced number of awakenings among adults with narcolepsy treated with Xywav. In adults with IH, Xywav treatment showed improvements in ESS and IH Severity Scale scores. Xywav is the only low-sodium oxybate, the #1 branded treatment for narcolepsy1 and the only U.S. Food and Drug Administration (FDA)-approved therapy to treat IH. Approximately 10,375 narcolepsy patients. Approximately 4,225 idiopathic hypersomnia (IH) patients, with 325 net patient adds. Xyrem (sodium oxybate) oral solution and high-sodium oxybate authorized generic (AG) royalties: Xyrem net product sales decreased 42% to $37.2 million in 1Q25 compared to 1Q24. Royalties from high-sodium oxybate AGs were $48 .9 million in 1Q25. Epidiolex/Epidyolex® (cannabidiol): Epidiolex/Epidyolex net product sales increased 10% to $217.7 million in 1Q25 compared to 1Q24. Outside of the U.S., Epidyolex is approved in more than 35 countries. Remain confident in achieving blockbuster status for Epidiolex/Epidyolex in 2025. Rylaze®/Enrylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales decreased 8% to $94.2 million in 1Q25 compared to 1Q24. This decrease was driven by headwinds from an update to Children's Oncology Group (COG) pediatric treatment protocols for acute lymphoblastic leukemia made in mid-2024 that impacted timing of asparaginase administration. The impact to Rylaze net product sales due to COG protocol updates is expected to normalize during 2Q25. Zepzelca (lurbinectedin): Zepzelca net product sales decreased 16% to $63.0 million in 1Q25 compared to 1Q24. This decrease was driven by increased competition in second-line (2L) small cell lung cancer (SCLC) and treatment protocol updates delaying progression in first-line (1L) limited-stage SCLC patients to the 2L setting. The Company submitted a supplemental New Drug Application (sNDA) for Zepzelca's use in combination with atezolizumab as maintenance therapy in 1L extensive-stage (ES) SCLC for patients who have not progressed after induction chemotherapy. Potentially practice-changing data from the Phase 3 IMforte trial, which showed a statistically significant and clinically meaningful benefit in both progression-free survival (PFS) and overall survival for the Zepzelca and atezolizumab combination for ES-SCLC patients receiving this treatment in the first-line maintenance setting, was accepted for an oral presentation at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting. This is the first presentation of data from the IMforte trial. Ziihera (zanidatamab-hrii): Ziihera net product sales were $2.0 million in 1Q25 following product launch in December 2024 . On April 25, 2025 , the Company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending the conditional marketing authorization of zanidatamab in 2L BTC (biliary tract cancer). The CHMP recommendation is being reviewed by the European Commission . __________________________ 1 Based on 1Q25 Xywav net product sales. Corporate Development Chimerix Acquisition: The Company completed its acquisition of Chimerix in April 2025 , adding dordaviprone to its late-stage pipeline. Dordaviprone is a novel first-in-class small molecule treatment in development for H3 K27M-mutant diffuse glioma, a rare, high-grade brain tumor that most commonly affects children and young adults. Key Pipeline Highlights Zanidatamab: The pivotal HERIZON-GEA-01 trial, evaluating zanidatamab in 1L gastroesophageal adenocarcinoma (GEA), is expected to read out in 2H25 based on the most recent assessment of progression events. Recruitment for the trial has been completed. New data from an ongoing Phase 2 trial of zanidatamab in combination with chemotherapy for the first-line treatment of HER2-positive metastatic GEA, including more mature overall survival data, was accepted for a rapid oral presentation at the 2025 ASCO Annual Meeting. 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. The Phase 2 pan-tumor trial to evaluate HER2-positive solid tumors continues to enroll patients. Dordaviprone: A New Drug Application for accelerated approval of dordaviprone in recurrent H3 K27M-mutant diffuse glioma was accepted and granted Priority Review by FDA. FDA has set a target Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025 . The ongoing Phase 3 ACTION trial is evaluating dordaviprone in newly diagnosed, non-recurrent H3 K27M-mutant diffuse glioma patients following radiation treatment, potentially extending its use into the first-line setting. Data on the efficacy and safety of dordaviprone from prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients was accepted for an oral presentation at the 2025 ASCO Annual Meeting. Financial Highlights Three Months Ended March 31 , (In thousands, except per share amounts) 2025 2024 Total revenues $ 897,841 $ 901,983 GAAP net loss $ (92,541) $ (14,618) Non-GAAP adjusted net income1 $ 105,233 $ 178,430 GAAP loss per share $ (1.52) $ (0.23) Non-GAAP adjusted EPS1 $ 1.68 $ 2.63 ____________________________ 1. Commencing with the first quarter of 2025, we are no longer including an adjustment for non-cash interest expense in the Company's non-GAAP adjusted financial measures and for the purposes of comparability, non-GAAP adjusted financial measures for the first quarter of 2024 have been updated to reflect this change. See "Non-GAAP Financial Measures" below. GAAP net loss for 1Q25 was $(92.5) million , or $(1.52) per diluted share, compared to $(14.6) million , or $(0.23) per diluted share, for 1Q24. Non-GAAP adjusted net income for 1Q25 was $105 .2 million, or $1.68 per diluted share, compared to $178 .4 million, or $2.63 per diluted share, for 1Q24. The GAAP net loss and non-GAAP adjusted net income for 1Q25 included an expense of $172.0 million related to certain Xyrem antitrust litigation settlements, which impacted our GAAP and non-GAAP results by $146.3 million (net of tax of $25.7 million ) or $2.38 per share on a GAAP basis and $2.34 per share on a non-GAAP adjusted basis. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release. Total Revenues Three Months Ended March 31 , (In thousands) 2025 2024 Xywav $ 344,804 $ 315,300 Xyrem 37,241 64,232 Epidiolex/Epidyolex 217,737 198,716 Sativex 5,407 2,735 Total Neuroscience 605,189 580,983 Rylaze/Enrylaze 94,233 102,750 Zepzelca 63,033 75,100 Defitelio/defibrotide 40,662 47,676 Vyxeos 29,544 32,023 Ziihera 1,975 — Total Oncology 229,447 257,549 Other 4,782 3,570 Product sales, net 839,418 842,102 High-sodium oxybate AG royalty revenue 48,946 49,947 Other royalty and contract revenues 9,477 9,934 Total revenues $ 897,841 $ 901,983 Total revenues for 1Q25 were in line with 1Q24. Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, was $654 .1 million in 1Q25, an increase of 4% compared to $630.9 million in 1Q24. The increase in 1Q25 was due to higher Xywav and Epidiolex/Epidyolex net product sales, partially offset by decreased Xyrem net product sales. Oncology net product sales were $229 .4 million in 1Q25, a decrease of 11% compared to $257 .5 million in 1Q24. The decrease in 1Q25 was primarily due to lower net product sales of Zepzelca, Rylaze/Enrylaze and Defitelio/defibrotide. In 1Q25, 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 March 31 , (In thousands, except percentages) 2025 2024 GAAP: Cost of product sales $ 104,620 $ 95,487 Gross margin 87.5 % 88.7 % Selling, general and administrative $ 514,013 $ 351,712 % of total revenues 57.2 % 39.0 % Research and development $ 180,652 $ 222,847 % of total revenues 20.1 % 24.7 % Acquired in-process research and development $ — $ 10,000 Income tax (benefit) expense1 $ (17,812) $ 11,669 Effective tax rate 1 16.2 % (728.4) % _________________________ 1. The GAAP income tax benefit in 1Q25 related primarily to the tax impact of certain Xyrem antitrust litigation settlements. The GAAP income tax expense in 1Q24 related primarily to tax shortfalls from share-based compensation. Three Months Ended March 31 , (In thousands, except percentages) 2025 2024 Non-GAAP adjusted: Cost of product sales $ 69,691 $ 64,148 Gross margin 91.7 % 92.4 % Selling, general and administrative $ 472,339 $ 311,499 % of total revenues 52.6 % 34.5 % Research and development $ 159,722 $ 204,015 % of total revenues 17.8 % 22.6 % Acquired in-process research and development $ — $ 10,000 Income tax expense1 $ 36,394 $ 64,735 Effective tax rate1 25.6 % 26.5 % _________________________ 1. The non-GAAP income tax expense decreased in the three months ended March 31, 2025 , compared to the same period in 2024, primarily due to the tax impact of certain Xyrem antitrust settlements in 1Q25. Changes in operating expenses in 1Q25 over the prior year period are primarily due to the following: Cost of product sales, on a GAAP and non-GAAP adjusted basis, increased in 1Q25 compared to the same period in 2024, primarily due to changes in product mix and higher inventory provisions. SG&A expenses, on a GAAP and non-GAAP adjusted basis, increased in 1Q25 compared to the same period in 2024, primarily due to certain Xyrem antitrust litigation settlements of $172.0 million incurred in 1Q25. Research and development (R&D) expenses, on a GAAP and non-GAAP adjusted basis, decreased in 1Q25 primarily due to lower clinical study costs primarily related to zanidatamab, as a result of timing of clinical trial activities, and JZP385 (essential tremor) and JZP150 (post-traumatic stress disorder) following discontinuation of these programs. Acquired in-process research and development (IPR&D) in 1Q24, on a GAAP and non-GAAP adjusted basis, related to an upfront payment made in connection with our asset purchase agreement with Redx Pharma plc . Cash Flow and Balance Sheet As of March 31, 2025 , cash, cash equivalents and investments were $2 .6 billion, and the outstanding principal balance of the Company's long-term debt was $5 .4 billion. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $885 .0 million. For the three months ended March 31, 2025 , the Company generated $429 .8 million 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. In April 2025 , the Company acquired Chimerix for a total consideration of approximately $935 million , which was funded with cash and cash equivalents. 2025 Financial Guidance1 Jazz Pharmaceuticals is updating its full year 2025 financial guidance primarily to reflect the impact of the Chimerix acquisition and certain Xyrem antitrust litigation settlements. Guidance provided as of (In millions) May 6, 2025 February 25, 2025 Total Revenues $4,150 - $4,400 $4,150 - $4,400 GAAP: (In millions, except per share amounts and percentages) May 6, 2025 February 25, 2025 Gross margin % 88 % 88 % SG&A expenses $1,640 - $1,723 $1,404 - $1,483 R&D expenses $835 - $895 $792 - $851 Acquired in-process research and development $870 - $900 2 - Effective tax rate 0% - 10% (5)% - 10% Net income (loss) $(615) - $(450) 3 $560 - $720 Net income (loss) per diluted share $(10.00) - $(7.50) 3 $9.15 - $11.50 Weighted-average ordinary shares used in per share calculations 61 - 62 62 - 63 Non-GAAP: (In millions, except per share amounts and percentages) May 6, 2025 February 25, 2025 Gross margin % 92%4,8 92 % SG&A expenses $1,470 - $1,530 5,8 $1,250 - $1,310 R&D expenses $760 - $810 6,8 $720 - $770 Acquired in-process research and development $870 - $900 2 - Effective tax rate 35% - 45%7,8 13% - 15% Net income $250 - $350 3,8 $1,400 - $1,500 Net income per diluted share $4.00 - $5.60 3,8 $22.50 - $24.00 Weighted-average ordinary shares used in per share calculations 62 - 63 62 - 63 ___________________________ 1. The Company's updated financial guidance includes the anticipated results of the acquired Chimerix operations from the date of acquisition April 21, 2025 . 2. Represents consideration allocated to IPR&D in the Chimerix acquisition, which the Company expects to account for as an asset acquisition. This guidance remains subject to final acquisition accounting adjustments. 3. The projected GAAP net loss and non-GAAP adjusted net income, include an acquired IPR&D expense relating to the acquisition of Chimerix of $885.0 million , at the midpoint, and certain Xyrem antitrust litigation settlements of $172.0 million , which are expected to impact the Company's GAAP and non-GAAP projected results by $1.0 billion (net of tax of $25.7 million ) or $16.64 per share on a GAAP basis and $16.50 per share on a non-GAAP adjusted basis. 4. Excludes $135-$155 million of amortization of acquisition-related inventory fair value step-up, $14-$16 million of share-based compensation expense and $1 million of integration related expenses. 5. Excludes $154-$173 million of share-based compensation expense and $16-$20 million of integration related expenses. 6. Excludes $72-$81 million of share-based compensation expense and $3-$4 million of integration related expense. 7. Excludes (35)% from the GAAP effective tax rate of 0%-10% relating to the income tax effect of adjustments between GAAP net loss and non-GAAP adjusted net income, resulting in a non-GAAP adjusted effective tax rate of 35%-45%. 8. See "Non-GAAP Financial Measures" below. Reconciliations of non-GAAP adjusted guidance measures are included above and in the table titled "Reconciliation of 2025 GAAP Net Loss And Diluted LPS To Non-GAAP Adjusted Net Income and Diluted EPS 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. IST ) to provide a business and financial update and discuss its 2025 first quarter results. 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 loss (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, commencing with the first quarter of 2025, the Company is no longer including an adjustment for non-cash interest expense in the Company's non-GAAP adjusted financial measures. For purposes of comparability, non-GAAP adjusted financial measures for the first quarter of 2024 have been updated to reflect this change. 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, including with respect to anticipated catalysts; expectations that Epidiolex will achieve blockbuster status in 2025; the ability to generate growth and long-term shareholder value; anticipated benefits and expenses relating to the Company's acquisition of Chimerix; the Company's advancement of pipeline programs and the timing of development activities, regulatory activities and submissions related thereto; the potential for a near-term commercial launch of dordaviprone in the U.S. if approved; the potential of the ongoing Phase 3 ACTION trial to confirm clinical benefit of dordaviprone in recurrent H3 K27M-mutant diffuse glioma and extend to use in first-line patients; 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 trade restrictions 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; the ability of the parties to obtain court approval of certain Xyrem class action settlement agreements and the risk that the Company may incur other charges or cash expenditures not currently contemplated due to unanticipated events that may occur, including in connection with certain Xyrem class action settlement agreements, and the risk that the Company is unable to reach settlement agreements with other Xyrem antitrust plaintiffs that are not party to certain Xyrem class action settlement agreements; 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, including Chimerix and the acquired product candidate dordaviprone; 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, including the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2025 . 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 LOSS(In thousands, except per share amounts)(Unaudited) Three Months Ended March 31 , 2025 2024 Revenues: Product sales, net $ 839,418 $ 842,102 Royalties and contract revenues 58,423 59,881 Total revenues 897,841 901,983 Operating expenses: Cost of product sales (excluding amortization of acquired developed technologies) 104,620 95,487 Selling, general and administrative 514,013 351,712 Research and development 180,652 222,847 Intangible asset amortization 154,448 155,730 Acquired in-process research and development — 10,000 Total operating expenses 953,733 835,776 Income (loss) from operations (55,892) 66,207 Interest expense, net (53,706) (66,116) Foreign exchange loss (213) (1,693) Loss before income tax (benefit) expense and equity in loss of investees (109,811) (1,602) Income tax (benefit) expense (17,812) 11,669 Equity in loss of investees 542 1,347 Net loss $ (92,541) $ (14,618) Net loss per ordinary share: Basic and diluted $ (1.52) $ (0.23) Weighted-average ordinary shares used in per share calculations - basic and diluted 60,979 62,537 JAZZ PHARMACEUTICALS PLC CONDENSED CONSOLIDATED BALANCE SHEETS(In thousands)(Unaudited) March 31 ,2025 December 31 ,2024 ASSETS Current assets: Cash and cash equivalents $ 1,861,946 $ 2,412,864 Investments 710,000 580,000 Accounts receivable, net of allowances 652,992 716,765 Inventories 492,776 480,445 Prepaid expenses 150,280 177,411 Other current assets 259,823 261,543 Total current assets 4,127,817 4,629,028 Property, plant and equipment, net 178,869 173,413 Operating lease assets 49,181 53,582 Intangible assets, net 4,718,158 4,755,695 Goodwill 1,760,045 1,716,323 Deferred tax assets, net 575,097 560,245 Deferred financing costs 8,999 9,489 Other non-current assets 116,516 114,482 Total assets $ 11,534,682 $ 12,012,257 LIABILITIES AND SHAREHOLDERS' EQUITY Current liabilities: Accounts payable $ 95,930 $ 77,869 Accrued liabilities 1,063,918 910,947 Current portion of long-term debt 31,000 31,000 Income taxes payable 31,762 18,757 Total current liabilities 1,222,610 1,038,573 Long-term debt, less current portion 5,336,481 6,077,640 Operating lease liabilities, less current portion 38,780 38,938 Deferred tax liabilities, net 670,801 676,736 Other non-current liabilities 91,119 86,614 Total shareholders' equity 4,174,891 4,093,756 Total liabilities and shareholders' equity $ 11,534,682 $ 12,012,257 JAZZ PHARMACEUTICALS PLC SUMMARY OF CASH FLOWS (In thousands)(Unaudited) Three Months Ended March 31 , 2025 2024 Net cash provided by operating activities $ 429,784 $ 267,229 Net cash used in investing activities (168,931) (271,904) Net cash used in financing activities (813,466) (56,552) Effect of exchange rates on cash and cash equivalents 1,695 (1,698) Net decrease in cash and cash equivalents $ (550,918) $ (62,925) JAZZ PHARMACEUTICALS PLC RECONCILIATIONS OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATION(In thousands, except per share amounts)(Unaudited) Three Months Ended March 31 , 2025 2024 NetIncome(Loss) DilutedEPS/(LPS)1 Net Income(Loss) Diluted EPS/(LPS)1 GAAP reported $ (92,541) $ (1.52) $ (14,618) $ (0.23) Intangible asset amortization 154,448 2.47 155,730 2.23 Share-based compensation expense 67,653 1.08 61,441 0.88 Acquisition accounting inventory fair value step-up 29,880 0.48 28,943 0.41 Income tax effect of above adjustments (54,207) (0.87) (53,066) (0.75) Effect of potentially dilutive ordinary shares on non-GAAP adjusted EPS1 — 0.04 — 0.09 Non-GAAP adjusted $ 105,233 $ 1.68 $ 178,430 $ 2.63 Weighted-average ordinary shares used in diluted per share calculations - GAAP1 60,979 62,537 Dilutive effect of employee equity incentive and purchase plans1 1,564 788 Dilutive effect of the 2026 Notes1 — 6,418 Weighted-average ordinary shares used in diluted per share calculations - non-GAAP1 62,543 69,743 ________________________________________________ Explanation of Adjustments and Certain Line Items: 1. Potentially dilutive ordinary shares from Jazz's employee equity incentive and purchase plans were excluded from the calculation of diluted loss per ordinary share, or LPS, on a GAAP basis, for the three months ended March 31, 2025 and March 31, 2024 because their effect would have been anti-dilutive. Diluted earnings per ordinary share, or EPS, was calculated using the "if-converted" method in relation to the 2.000% exchangeable senior notes due 2026, or the 2026 Notes. In July 2024 , we made the irrevocable election to net share settle the 2026 Notes. As a result, the assumed issuance of ordinary shares upon exchange of the 2026 Notes has only been included in the calculation of diluted EPS, on a non-GAAP adjusted basis, in the three months ended March 31, 2024 . The potential issue of ordinary shares upon exchange of the 2026 Notes was anti-dilutive and had no impact on GAAP reported LPS for the three months ended March 31, 2024 . JAZZ PHARMACEUTICALS PLC RECONCILIATIONS OF GAAP REPORTED TO NON-GAAP ADJUSTED INFORMATIONCERTAIN LINE ITEMS - FOR THE THREE MONTHS ENDED MARCH 31, 2025 (In thousands, except percentages)(Unaudited) Three months ended March 31, 2025 Cost of productsales Gross margin Selling, general and administrative Research and development Intangible asset amortization Interestexpense,net Income tax(benefit) expense Effective tax rate GAAP Reported $ 104,620 87.5 % $ 514,013 $ 180,652 $ 154,448 $ 53,706 $ (17,812) 16.2 % Non-GAAP Adjustments: Intangible asset amortization — — — — (154,448) — — — Share-based compensationexpense (5,049) 0.6 (41,674) (20,930) — — — — Acquisition accounting inventoryfair value step-up (29,880) 3.6 — — — — — — Income tax effect of aboveadjustments — — — — — — 54,206 9.4 Total of non-GAAP adjustments (34,929) 4.2 (41,674) (20,930) (154,448) — 54,206 9.4 Non-GAAP Adjusted $ 69,691 91.7 % $ 472,339 $ 159,722 $ — $ 53,706 $ 36,394 25.6 % Three months ended March 31, 2024 Cost ofproduct sales Gross margin Selling, general and administrative Research and development Intangibleasset amortization AcquiredIPR&D Interestexpense, net Income taxexpense Effectivetax rate GAAP Reported $ 95,487 88.7 % $ 351,712 $ 222,847 $ 155,730 $ 10,000 $ 66,116 $ 11,669 (728.4) % Non-GAAP Adjustments: Intangible asset amortization — — — — (155,730) — — — — Share-based compensation expense (2,396) 0.3 (40,213) (18,832) — — — — — Acquisition accountinginventory fair value step-up (28,943) 3.4 — — — — — — — Income tax effect of aboveadjustments — — — — — — — 53,066 754.9 Total of non-GAAPadjustments (31,339) 3.7 (40,213) (18,832) (155,730) — — 53,066 754.9 Non-GAAP Adjusted $ 64,148 92.4 % $ 311,499 $ 204,015 $ — $ 10,000 $ 66,116 $ 64,735 26.5 % JAZZ PHARMACEUTICALS PLC RECONCILIATION OF 2025 GAAP NET LOSS AND DILUTED LPS TO NON-GAAP ADJUSTED NET INCOME AND DILUTEDEPS GUIDANCE(In millions, except per share amounts)(Unaudited) Net Income(Loss) DilutedEPS/(LPS) GAAP $(615) - $(450) $(10.00) - $(7.50) Intangible asset amortization 610 - 660 9.70 - 10.60 Share-based compensation expense 240 - 270 3.80 - 4.35 Acquisition accounting inventory fair value step-up 135 - 155 2.15 - 2.50 Integration related expense 20 - 25 0.30 - 0.40 Income tax effect of above adjustments (215) - (235) (3.40) - (3.75) Effect of potentially dilutive ordinary shares on non-GAAP adjusted EPS - 0.15 Non-GAAP adjusted $250 - $350 $4.00 - $5.60 Weighted-average ordinary shares used in per share calculations - GAAP 61 - 62 Weighted-average ordinary shares used in per share calculations - non-GAAP 62 - 63 The Company's 2025 financial guidance includes the anticipated results of the acquired Chimerix operations from the date of acquisition April 21, 2025 and an acquired IPR&D expense as a result of the Company's expected accounting treatment of Chimerix as an asset acquisition. This guidance remains subject to final acquisition accounting. 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-first-quarter-2025-financial-results-and-updates-2025-financial-guidance-302447694.html SOURCE Jazz Pharmaceuticals plc

前言：近日，一起突如其来的收并购点燃了美股投资者：Jazz Pharmaceuticals（Nasdaq:Jazz）和Chimerix（Nasdaq:CMRX）宣布两家公司已达成最终协议，Jazz将以每股8.55美元的现金收购Chimerix，总对价约为9.35亿美元。该交易已获得两家公司的批准，预计将于2025年第二季度完成。 要知道，这场交易前一天的股价也不过5美元出头，也就是说，本次收购费用几乎翻了CMRX的一倍。CMRX的管线确实不算大众，但能让Jazz看上并溢价90%以上进行收购，必定有其独特的魅力。而收购之后的Jazz，又有哪些看点？ 01 CMRX的管线 CMRX的管线来看，目前能进行估值的管线只有一条——ONC201。该条管线目前也已经冲破重重艰难险阻就快修成正果，到了FDA上市审批（NDA）的阶段。这条管线从第一次开始临床试验（first man）到现在，已经历经10余载，从中也能看出小biotech从头走过来到被收购的完整历程。 （图片来源：CMRX官网） ONC201靶向DRD2和ClpP，主要治疗的患者是患有携带H3K27M突变的复发型胶质瘤患者。众所周知，胶质瘤按照危险程度一共分为I-IV级，III级和IV级是高级别胶质瘤，当外科手术切除之后复发，目前非常缺乏治疗手段。当现治疗“癌王”胰腺癌的药物不断涌现进行临床患者招募，治疗高级别胶质瘤却处于一筹莫展的境况。 该突变方面，在临床上，H3 K27M突变的肿瘤通常处于上文所说的IV级，预后较差。如图所示，在位于脑桥的胶质瘤中，携带这种突变的比率高达75%，而位于脑室的胶质瘤中，携带这种突变的比率也高达71%；此外，约10%的成人神经胶质瘤也显示H3 K27M突变。 （图片来源：CMRX官网PPT） 人数方面，全美国每年约有21000人被诊断为胶质瘤，其中大约有2000名患者受到H3 K27M突变的影响。市场的整体情况大致如此。 而ONC21的机制方面，它的机制也确实非常非常有意思。它一方面可以激动ClpP（Clp蛋白酶蛋白水解亚基）。ClpP是胶质瘤中线粒体的蛋白酶，可以降解线粒体呼吸链蛋白以破坏能量稳态，而胶质瘤的繁殖自然需要大量的能量来进行支撑，因此，破坏能量稳态对影响其增殖起到了重要的作用。也正因为此，在治疗过程中，ClpP会作为重要的biomarker存在。 另一方面，ONC21其实一开始被发现的机制并不是激动ClpP，而是拮抗多巴胺受体D2 (DRD2)，关于这条通路是怎样影响肿瘤的，目前尚不是很清楚，但DRD2是一种G蛋白偶联受体，它可以调节Ras通路；而RAS-RAF-MEK-ERK（简称ERK信号通路）是调控细胞增殖与存活的核心通路，其异常活化与多种癌症的发生发展密切相关。阻断上游Ras信号，对抑制肿瘤活化增殖，促进细胞凋亡也许有意想不到的作用。 但具体ONC21通过DRD2是怎么抑制肿瘤，目前研究并不算很透彻。这大致是目前机制上的情况。 目前能看到的是早期临床试验数据，总量人数为50人。在高级胶质瘤方面，ORR为20%，低级别胶质瘤方面，ORR为26%，以RNAO2.0评估的胶质瘤疗效标准方面，ORR为28%。 该药很早就获得了快速通道资格和孤儿药认定，而目前已经走到了申报上市这一步，相信之后的东西，也会是水到渠成。 02 Jazz近况 Jazz作为一家pharma而言市值并不算很高，甚至没有单一管线的summit高，目前市值为84亿美元左右；它的成名来源与对大麻素的销售，是全球著名的大麻素销售巨头。 其核心单品为Epidiolex，它是第一个也是唯一一个获得FDA 批准的处方大麻二酚 (CBD)， 用于治疗1岁或以上患者与Lennox-Gastaut综合征(LGS)、Dravet综合征或结节性硬化症 (TSC)相关的癫痫发作。它来自于2021年一桩巨额收购案：Jazz以72亿美元收购GW pharma。 其相关的大麻类药物还有satyivex。除此之外，其在2005年收购了Orphan Medical，拿到了羟基丁酸钠这款药物，用于治疗白天嗜睡。 除了上述的精神类药物，Jazz在其它领域也有浓墨重彩的商业化布局。例如defitelio（去纤维钠）治疗肝窦阻塞综合征，RYLAZE治疗大肠杆菌衍生的天冬酰胺酶过敏的成人和1个月或以上的小儿患者的急性淋巴细胞白血病(ALL) 和淋巴母细胞淋巴瘤 (LBL)等。 如图所示为Jazz的营收情况，2023年，其营收达到了38.34亿美元， 总体而言，从现在Jazz的商业化版图来看，它的营收主要还是来自于精神类药物，尤其是大麻类药物，为此也产生过不少专利纠纷，除了精神类药物之类的商业化单品很杂，给人一种不太成体系的感觉。 （图片来源：Jazz 2023年年报） 然而从研发管线上来看，却可以看到Jazz拼尽全力向肿瘤领域转型的决心，如果不去看商业化板块，只去看管线，甚至会以为它是一家正在起步推进管线的肿瘤biotech。 其中，其肿瘤的首发管线Zanidatamab在2024年底已经被FDA批准，进入了上市阶段。该管线是一条HER2双表位抗体，也是Jazz渴望转型的一个体现：2022年，Jazz从zymwok以5000万美元的一次性付款，3.75亿美元的预付款引进该管线，且总交易金额达到了17.6亿美元。 目前，该BD算是有了初步结果，结出的第一个获批适应症二线治疗胆管癌，目前一线治疗胆管癌，一线治疗胃食管腺癌等也已经进入了三期临床阶段，二期临床还有乳腺癌等大适应症在持续推进。 该单品的商业化进程预计将会波澜壮阔。 除此之外，化疗药物芦比卡定也已经获得了批准上市，该药是Jazz通过从PharmaMar手中BD获得，目前用于治疗小细胞肺癌。JZP351则是一种化疗药物组合，目前在治疗白血病的III期临床阶段。 可以看到，Jazz一边收购大麻巨头获得稳健的营收保障，一边不断进行肿瘤药物的BD，用于后续管线的布局，让公司看起来充满预期。 03 结语 从上述对两家企业的叙述中，本次收购就显得合理了起来，Jazz渴望进一步充实肿瘤管线，它在拥有HER2双抗这项大分子肿瘤药物，已经几款化疗药物药物之后，选择了一家小分子biotech进行收购，一方面是让肿瘤管线看起来更加多元化，另一方面也确实是选择了剑走偏锋的差异化竞争。 除此之外，后续管线的潜力也不容小觑：首当其冲的是后续管线ONC206，它是ONC201的下一代同靶点药物，体外活性是ONC201的10倍，拥有非常强劲的体外抗肿瘤活性，目前临床剂量递增试验已经完成。 ONC212和CMX521都在有序推进之中。 总体来说这次收购是Jazz的一次为了扩张肿瘤板块而进行的又一次大动作，既在意料之外，又在情理之中。CMRX也提前上岸，是非常不错的biotech结局。 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。